Topical antimicrobial compositions and methods of formulating the same

ABSTRACT

A method of treating a bacterial infection of a subject includes topically administering a topical composition that includes nitrofurantoin combined with a carrier. The topical composition may be administered by contacting a tissue surface of the subject to be treated with the topical composition such as skin or mucosal tissue.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation in-part application ofco-pending U.S. patent application Ser. No. 15/881,009, filed Jan. 26,2018, and is also a continuation in-part application of co-pending U.S.Patent Application No. 16/270,335, filed Feb. 7, 2019, each of which ishereby incorporated by reference in its entirety. U.S. patentapplication Ser. No. 15/881,009 is a continuation in-part of U.S. patentapplication Ser. No. 15/625,989, filed Jun. 16, 2017, which is acontinuation-in-part of U.S. patent application Ser. No. 14/975,172 (nowU.S. Pat. No. 9,707,229), filed Dec. 18, 2015, and U.S. patentapplication Ser. No. 15/440,800, filed Feb. 23, 2017. U.S. patentapplication Ser. No. 16/270,335 is a continuation-in-part of U.S. patentapplication Ser. No. 15/976,579, filed May 10, 2018, which is acontinuation-in-part of U.S. patent application Ser. No. 14/990,168,filed Jan. 7, 2016, U.S. patent application Ser. No. 15/597,936 (nowU.S. Pat. No. 10,105,342), filed May 17, 2017, and U.S. patentapplication Ser. No. 15/668,184, filed Aug. 3, 2017. U.S. patentapplication Ser. No. 15/597,936 is a continuation-in-part application ofU.S. patent application Ser. No. 15/440,800, filed Feb. 23, 2017, U.S.patent application Ser. No. 14/975,172, (now U.S. Pat. No. 9,707,229)filed Dec. 18, 2015, and U.S. patent application Ser. No. 14/819,342,filed Aug. 5, 2015. U.S. patent application Ser. No. 15/440,800 claimsthe benefit of U.S. Provisional Patent Application No. 62/298,991, filedFeb. 23, 2016, and U.S. Provisional Patent Application No. 62/289,994,filed Feb. 23, 2016. U.S. patent application Ser. No. 15/668,184 claimsthe benefit of U.S. Provisional Patent Application No. 62/370,571, filedon Aug. 3, 2016. Each of the provisional and nonprovisional patentapplications listed above is hereby incorporated by reference in itsentirety.

TECHNICAL FIELD

The present application relates to compounded compositions, methods ofmaking compounded compositions, and methods of using compoundedcompositions to treat or prevent an infection. The present applicationalso relates to antimicrobial agents and methods of using antimicrobialagents to treat or prevent an infection.

BACKGROUND

The body normally serves as host for a variety of bacteria and fungi.Most of the time, the balance between the body as host and themicroorganisms is maintained. However, there are times when thephysiological, biochemical, and/or environmental conditions permit themicroorganisms to tip that balance, thereby causing an infection.

Foot infections can be difficult problems for physicians to treatbecause of the biomechanical complexities of the extremity and theunderlying circumstances that cause the infections. Soft tissueinfections in the foot consist of any infectious process affecting theskin, subcutaneous tissue, adipose tissue, superficial or deep fascia,ligaments, tendons, tendon sheaths, joints, and/or joint capsules.Considering that there are more than 20 joints, 44 tendons,approximately 100 ligaments, 4 major compartments, and numerous fascialplanes in the normal foot, the potential for complex problems is high.

Bacterial infections of the feet can occur as collections of pus, suchas an abscess following a puncture wound or an infected hair follicle.These types of infections are usually red and elevated, and sometimescan be mistaken for an insect bite. There are many types of bacteriathat cause an abscess, but staph are a leading cause. Bacterial skininfections can also resemble a rash, appearing as a reddened, tender,and warm area of skin. This type of infection is called cellulitis andcan spread quickly, leading to red streaks that move from the foottoward the leg. The appearance of streaks is known as lymphangitis,which means the infection is spreading toward the lymph nodes.Cellulitis and lymphangitis can be caused by a variety of types ofbacteria, but staph and sometimes streptococcus are the most commoncauses. Any infection, especially cellulitis and lymphangitis, requiresprompt medical attention to avoid further spreading and complications.If left untreated, then some infections can spread to deeper tissues,including bone.

Certain fungal infections of the skin known as tinea infections arecaused by dermatophytes, which are members of the Trichophyton,Microsporum, and Epidermophyton species. These mold-like fungi thrive inwarm, moist areas, thriving on the dead tissues of hair, nails, andouter skin layers. Tinea infections include tinea pedis, known asathlete's foot; tinea corporis, known as ringworm; tinea capitis, afungal infection of the scalp that can cause hair loss; tinea cruris,known as jock itch or tinea of the groin; tinea unguum, which is tineaof the nails; and tinea versicolor, a superficial fungal infection thatproduces brown, tan, or white spots on the trunk of the body. Tineainfections are contagious and can be passed through direct contact or bycontact with clothing, from shower and pool surfaces, and even frompets.

Athlete's foot or tinea pedis is by far the most common form, with morethan 12 million people in the United States suffering from the diseaseper year. It presents with redness, itching, burning, cracking, scaling,swelling, and occasionally bleeding. Athlete's foot includes toe webinfections, moccasin type infections, and vesicular type infections. Thecondition generally includes small vesicles, fissures, scaling,maceration, hyper keratinization, and eroded areas between the toes andon the plantar surface of the foot, as well as on other skin areas. Forexample, the nails may show thickening, pitting, and subungual debris.

Reoccurrences of the infection are frequent. For some subjects, such asthose also diagnosed with diabetes or circulatory problems, or obesesubjects, tinea infections and their treatment can be quite serious. Thesource of the affliction often is a public safety and health concern, asthe occurrence of tinea pedis is higher in public areas such as lockerrooms, public showers, sports facilities, and the like.

Moreover, there are at least three different types of nail infectionscaused by fungi. The most common infection is frequently caused byTrichophyton rubrum and affects the nail bed and the area beneath thenail. Another type of infection affects only the nail surface andcreates white or light colored patches. This second type of fungalinfection is unusual and represents only about 10% of the reportedcases. A third type of fungal infection affects the nail root andusually afflicts persons with impaired immune defense. A fourth (andunusual) type is caused by an infection of yeast fungi. Infections byyeast most often only affect nails that already are infected or damagedin some way.

Fungi are invasive to keratin nail tissue. Apart from becomingdiscolored and brittle, the nail may often separate from the nail bed.In addition, pain and difficulty in wearing foot apparel is oftenexperienced. Initially, the disease affects only one nail, typically onenail of the foot, and is thereafter spread to more nails. The palms ofthe hands and the soles of the feet may frequently be affected as well.When the skin is affected, red spots frequently occur and the skin maypeel off. Nail fungal infections are one of the hardest forms ofexternal infection to treat, of which infections of toe nails are themost difficult to treat.

Wound healing is another area impacted by microbial organisms. Woundhealing is a complex and dynamic process in which tissues repair fromdamage. The process generally includes a hemostasis phase, aninflammation phase, a granulation tissue formation phase, and a tissueremodeling phase. Wounds may occur from broken or unbroken skin as aresult of blunt trauma, punctures, excessive exposure to cold or heat,chemical exposure, radiation exposure, and surgical procedures. Woundsmay also arise as itching, scaling, swelling, or blistering of the skin.Wounds may also arise from eczemas, chronic skin conditions such aspsoriasis, rosacea, and conditions accompanying bacterial, viral, orfungal infections may also damage skin.

Many factors can complicate or interfere with normal adequate woundhealing. For example, such factors include age, infection, poornutrition, immunosuppression, medications, radiation, diabetes,peripheral vascular disease, systemic illness, smoking, or stress.Abnormal wound healing can increase susceptibility to local infection,which also increases the risk systemic infection. What is needed areadditional and alternative wound healing compositions for the treatmentof wounds.

Despite advances in the understanding of the pathology of bacterialinfections and fungal infections, there is still a need for compositionsand methods that efficiently treat or prevent the progression andreoccurrence of bacterial infections and/or fungal infections thataffect at least part of one or both feet.

SUMMARY

In one aspect, a method of treating a bacterial infection of a subjectincludes topically administering a topical composition that includesnitrofurantoin combined with a carrier. The topical composition may beadministered by contacting a tissue surface of the subject to be treatedwith the topical composition such as skin or mucosal tissue.

In various embodiments, the topical composition may be administered in adosage amount of between approximately 25 mg and approximately 200 mgnitrofurantoin. The topical composition may be topically administeredonce or twice daily. In one example, the topical composition may betopically administered twice daily and the topical composition comprisesbetween approximately 50 mg and approximately 200 mg nitrofurantoin ineach topical administration.

In some embodiments, the carrier comprises an aqueous solution and thetopical composition comprises a solution format. In one example, thetissue surface comprises an ear of the subject and administering thetopical composition comprises administering the solution to an ear canalin one or more drops. In another example, the tissue surface comprises alung of the subject and administering the topical composition comprisesnebulizing the solution for inhalation by the subject to deliver thetopical composition to an infected mucosal tissue of the lung. In yetanother example, the tissue surface comprises a nasal cavity of thesubject and administering the topical composition comprises contactinginfected mucosal tissue of the nasal cavity via irrigation, spray, ornasal nebulization. In still yet another example, the tissue surfacecomprises a vagina or anus of the subject and administering the topicalcomposition comprises contacting infected mucosal tissue of the vaginaor anus with the solution. In another example, the tissue surfacecomprises a mouth of the subject and administering the topicalcomposition comprises contacting infected mucosal tissue of the mouthwith the solution. In yet another example, the infected surfacecomprises skin of the subject, and wherein administering the topicalcomposition comprises spraying the solution onto the infected skinsurface, irrigating the infected skin surface with the solution, orsubmerging the infected skin surface in the solution.

In some embodiments, the carrier comprises an ointment, cream, gel, orlotion and the topical composition is formulated in an ointment, cream,gel, or lotion format. In one example, the tissue surface comprises avagina or anus of the subject and administering the topical compositioncomprises applying the ointment, cream, gel, or lotion onto the infectedmucosal tissue of the vagina or anus. In another example, the tissuesurface comprises a mouth of the subject and administering the topicalcomposition comprises applying the ointment, cream, gel, or lotion ontoinfected mucosal tissue of the mouth. In still another example, thetissue surface comprises skin of the subject and administering thetopical composition comprises applying the ointment, cream, gel, orlotion onto the infected skin surface.

In some embodiments, the carrier comprises a powder and the topicalcomposition comprises a powder format. In one example, the tissuesurface comprises mucosal tissue and administering the topicalcomposition comprises applying the powder onto the infected mucosaltissue. In another example, the infected mucosal tissue is mucosaltissue of the lungs, nasal cavity, mouth, vagina, or anus. In stillanother example, the tissue surface comprises skin of the subject andadministering the topical composition comprises applying the powder ontothe infected skin.

DESCRIPTION

The present disclosure describes compounded compositions for topicaladministration. A compounded composition according to the presentdisclosure may include a topical composition formulated for topicaladministration to an external surface of a mammal, such as a human. Insome embodiments, the topical composition may be formulated to treatinfections or suspected infections of tissues and may be topicallyadministered to surface tissues comprising or adjacent tissues thereof,which may include nails, wounded tissue, mucosal surfaces of the vaginaor anus, skin such as on hands, feet, scalp, torso, arms, legs, or othersurface. Embodiments of the composition may also be formulated to beapplied to nails, a vaginal orifice, or anal orifice. Embodiments of thecomposition may be formulated for topical application tissues of a nose,mouth, e.g., mouth rinse, wash, or gargle, lung, or ear. Such acomposition may be referred to herein as a topical composition.

The topical composition may generally include an antimicrobial agentcomprising one or more pharmaceuticals drugs. Some embodiments mayinclude combinations of active agents described herein without theantimicrobial agent. The topical composition may include a carriercomprising one or more carrier components. Unless stated otherwise,carrier is intended to include carrier component such that use of theterm carrier may refer to a component of the carrier and is notrestrictive in that other carrier components may be included and thecarrier component referred to as the carrier need not form a completecarrier. Indeed, a carrier may include a thickening agent added to acommercially available medicated carrier solution, lotion, or cream,alone or together with other carriers, to formulate a carrier withrespect to the topical composition. Carrier may also be usedinterchangeably with the term base. Carrier may refer to a diluentand/or medium within which active agents are dissolved, suspended, ordispersed. The carrier may be liquid, semiliquid, or solid. For example,the carrier may include an aqueous, organic, or inorganic solution,which may include a suspension/dispersion, cream, gel, ointment, lotion,emulsion, powder, or paste. The topical composition may be formulated totreat microbial infections, such as infections of the skin, nails,mucosal surfaces (such as mucosal surfaces of vulva, vagina, anus, nose,mouth, ear, pharynx, upper respiratory tract, lungs), and potentiallyinternalized infections, e.g., via transdermal administration ofantimicrobial agents.

Embodiments of the topical composition may include an antimicrobialagent selected from an antibacterial component, antifungal component, orboth. In one embodiment, the antibacterial component may include anantiviral component comprising one or more antiviral pharmaceuticaldrugs. As introduced above, the topical composition may comprise theantimicrobial agent alone or in combination with one or more additionalactive agents selected from an anti-inflammatory agent, steroid agent,anti-allergic agent, anti-depressant agent, stimulant agent,disinfectant agent, mucolytic agent, anticonvulsant agent, localanesthetic agent, or combinations thereof. In one embodiment, thetopical composition includes additional active agents selected from oneor more anticonvulsants, nerve depressants, muscle relaxants, NMDA(N-Methyl-D-aspartate) receptor antagonists, opiate or opioid agonists,antidepressants, and/or other active agents. In some embodiments, thetopical composition may comprise the antimicrobial agent including anantifungal component, antibacterial component, or both alone or incombination with a steroid agent, antiviral agent, NSAID agent,antidepressant agent, anticonvulsant agent, analgesic agent, opiate oropioid agonist agent, keratolytic agent, or combination thereof.

It is to be appreciated that recitations herein of activepharmaceuticals include pharmaceutical equivalents such aspharmaceutically acceptable salts thereof whether or not specificallyrecited as such. Similarly, recitation of a particular activepharmaceutical salt may also include other pharmaceutically acceptablesalts thereof whether or not specifically recited as such.

In various embodiments, the antimicrobial agent comprises an antifungalcomponent, alone or in combination with an antibacterial component,wherein the an antifungal component includes one or more antifungalpharmaceutical drugs selected from one or more categories of antifungalcomponents including azoles (imidazoles), antimetabolites, allylamines,morpholine, glucan synthesis inhibitors (echinocandins), polyenes,benoxaaborale; other antifungal/onychomycosis agents, and new classes ofantifungal/onychomycosis agents. For example, the antifungal componentmay comprise one or more antifungals selected from abafungin,albaconazole, amorolfin, amphotericin b, anidulafungin, bifonazole,butenafine, butoconazole, candicidin, caspofungin, ciclopirox,clotrimazole, econazole, fenticonazole, filipin, fluconazole,flucytosine, griseofulvin, haloprogin, hamycin, isavuconazole,isoconazole, itraconazole, ketoconazole, micafungin, miconazole,naftifine, natamycin, nystatin, omoconazole, oxiconazole, polygodial,posaconazole, ravuconazole, rimocidin, sertaconazole, sulconazole,terbinafine, terconazole, tioconazole, tolnaftate, undecylenic acid,voriconazole, or a combination thereof. In some embodiments, theantibacterial component is selected from one or more azoles. In oneexample, the antifungal component is selected from itraconazole,voriconazole, or combination thereof. In various embodiments, theantimicrobial agent comprises an antifungal component selected from oneor more antifungals comprising fluconazole, itraconazole, voriconazole,amphotericin, nystatin, clotrimazole, econazole, or ketoconazole.

In various embodiments, the topical composition may comprise betweenapproximately 0.01% and approximately 20% by weight antifungalcomponent, such as between approximately 0.01% and approximately 5%,approximately 0.01% and approximately 3%, approximately 0.01% andapproximately 1%, approximately 0.01% and approximately 0.25%,approximately 0.01% and approximately 0.15%, approximately 0.05% andapproximately 0.15%, between 0.1% and 10%, approximately 0.1% andapproximately 0.5%, approximately 0.1% and approximately 0.2%,approximately 0.2% and approximately 0.8%, approximately 0.2% andapproximately 0.6%, approximately 0.2% and approximately 0.4%,approximately 0.3% and approximately 1%, approximately 0.3% andapproximately 0.8%, approximately 0.3% and approximately 0.6%,approximately 0.4% and approximately 1%, approximately 0.5% andapproximately 1%, approximately 0.5% and approximately 8%, approximately0.6% and approximately 1%, approximately 0.6% and approximately 0.8%,approximately 0.8% and approximately 1%, approximately 1% andapproximately 3%, approximately 1% and approximately 10%, approximately1% and approximately 8%, approximately 1% and approximately 5%,approximately 1% and approximately 3%, approximately 3% andapproximately 10%, approximately 3% and approximately 8%, approximately3% and approximately 5%, between 5% and 10%, approximately 5% andapproximately 8%, approximately 6% and approximately 10%, approximately6% and approximately 8%, approximately 7% and approximately 10%,approximately 8% and approximately 10%, approximately 10% andapproximately 20%, approximately 10% and approximately 15%,approximately 10% and approximately 12%, approximately 12% andapproximately 15%, or between approximately 15% and approximately 20%antifungal component by weight. In some embodiments, the amount ofantifungal component by weight may be approximately 0.01%, approximately0.05%, approximately 0.1%, approximately 0.5%, approximately 1%,approximately 1.5%, approximately 2%, approximately 2.5%, approximately3%, approximately 3.5%, approximately 4%, approximately 4.5%,approximately 5%, approximately 5.5%, approximately 6%, approximately6.5%, approximately 7%, approximately 7.5%, approximately 8%,approximately 8.5%, approximately 9%, approximately 9.5%, approximately10%, approximately 11%, approximately 12%, approximately 13%,approximately 14%, approximately 15%, approximately 17%, approximately19%, approximately 20%, or any other percentage between approximately0.01% and 20% by weight of the topical composition.

In various embodiments, the topical composition comprises anantimicrobial agent including an antifungal component alone or incombination with an anti-inflammatory agent, an non-steroidalanti-inflammatory (NSAID) agent, an anti-allergic agent, anantimicrobial agent, an anti-depressant agent, a stimulant agent, adisinfectant agent, an anticonvulsant agent, a local anesthetic agent,or combination thereof, which may include one or more activepharmaceutical drugs of selected agents or components thereof. In oneembodiment, the topical composition includes one or more additionalactive agents selected from one or more anticonvulsants, nervedepressants, muscle relaxants, NMDA (N-Methyl-D-aspartate) receptorantagonists, opiate or opioid agonists, antidepressants, and/or otheractives. In some embodiments, the topical composition comprises anantifungal component alone or in combination with an antibacterialcomponent, antiviral component, steroid agent, NSAID agent,antidepressant agent, anticonvulsant agent, mucolytic agent, analgesicagent, opioid agent, keratolytic agent, or combination thereof, whichmay include one or more active pharmaceutical drugs of selectedcomponents or agents. In an above or another embodiment, theantimicrobial agent may further comprise an antibacterial componentcomprising one or more antibacterial pharmaceutical drugs, such as thoseidentified herein.

The antimicrobial agent may comprise an antibacterial component alone orin combination with an antifungal component. In some embodiments, theantibacterial component comprises one or more enicillins,cephalosporins, fluoroquinolones, aminoglycosides, monobactams,carbapenems, macrolides, other antibacterial, or combination thereof.For example, the antibacterial component may include one or moreantibacterial pharmaceutical drugs selected from afenide, amikacin,amoxicillin, ampicillin, arsphenamine, azithromycin, azlocillin,aztreonam, bacampicillin, bacitracin, carbacephem (loracarbef),carbenicillin, cefaclor, cefadroxil, cefalotin, cefamandole, cefazolin,cefdinir, cefditoren, cefepime, cefixime, cefoperazone, cefotaxime,cefoxitin, cefpodoxime, cefprozil, ceftazidime, ceftibuten, ceftizoxime,ceftobiprole, ceftriaxone, cefuroxime, cephalexin, chloramphenicol,chlorhexidine, ciprofloxacin, clarithromycin, clavulanic acid,clindamycin, cloxacillin, colimycin, colistimethate teicoplanin,colistin, demeclocycline, dicloxacillin, dirithromycin, doripenem,doxycycline, efprozil, enoxacin, ertapenem, erythromycin, ethambutol,flucloxacillin, fosfomycin, furazolidone, gatifloxacin, geldanamycin,gentamicin, grepafloxacin, herbimycin, imipenem, isoniazid, kanamycin,levofloxacin, lincomycin, linezolid, lomefloxacin, meropenem,methicillin, meticillin, mezlocillin, minocycline, mitomycin,moxifloxacin, mupirocin, nafcillin, neomycin, netilmicin,nitrofurantoin, norfloxacin, ofloxacin, oxacillin, oxytetracycline,paromomycin, penicillin G, penicillin V, piperacillin, pivmecillinam,platensimycin, polymyxin B, prontosil, pvampicillin, pyrazinamide,quinupristin/dalfopristin, rifampicin, rifampin, roxithromycin,sparfloxacin, spectinomycin, spiramycin, sulbactam, sulfacetamide,sulfamethizole, sulfamethoxazole, sulfanilamide, sulfanilimide,sulfisoxazole, sulphonamides, sultamicillin, telithromycin,tetracycline, thiamphenicol, ticarcillin, tobramycin, trimethoprim,trimethoprim-sulfamethoxazole, troleandomycin, trovafloxacin, or acombination thereof. In some embodiments, the antibacterial component isselected from mupirocin, gentamycin, tobramycin, or combinationsthereof. In one embodiment, the antibacterial component includes anaminoglycoside.

In various embodiments, the antimicrobial agent comprises anantibacterial component selected from one or more antibacterial drugscomprising vancomycin, ciprofloxacin, levofloxacin, azithromycin,clindamycin, mupirocin, doxycycline, mupirocin, ceftriaxone,colistimethate, tobramycin, cefepime, gentamicin, streptomycin,sulfamethoxazole/trimethoprim. In one example, the topical compositioncomprises linezolid, levofloxacin, ciprofloxacin, or combinationthereof. In an embodiment, the antimicrobial agent comprises cefixime,nitrofurantoin, tetracycline, or combination thereof.

In various embodiments, the topical composition may comprise betweenapproximately 0.01% and approximately 20% by weight antibacterialcomponent, such as between approximately 0.01% and approximately 5%,approximately 0.01% and approximately 3%, approximately 0.01% andapproximately 1%, approximately 0.01% and approximately 0.25%,approximately 0.01% and approximately 0.15%, approximately 0.05% andapproximately 0.15%, between 0.1% and 10%, approximately 0.1% andapproximately 0.5%, approximately 0.1% and approximately 0.2%approximately 0.2% and approximately 0.8%, approximately 0.2% andapproximately 0.6%, approximately 0.2% and approximately 0.4%,approximately 0.3% and approximately 1%, approximately 0.3% andapproximately 0.8%, approximately 0.3% and approximately 0.6%,approximately 0.4% and approximately 1%, approximately 0.5% andapproximately 1%, approximately 0.5% and approximately 8%, approximately0.6% and approximately 1%, approximately 0.6% and approximately 0.8%,approximately 0.8% and approximately 1%, approximately 1% andapproximately 3%, approximately 1% and approximately 10%, approximately1% and approximately 8%, approximately 1% and approximately 5%,approximately 1% and approximately 3%, approximately 3% andapproximately 10%, approximately 3% and approximately 8%, approximately3% and approximately 5%, between 5% and 10%, approximately 5% andapproximately 8%, approximately 6% and approximately 10%, approximately6% and approximately 8%, approximately 7% and approximately 10%,approximately 8% and approximately 10%, approximately 10% andapproximately 20%, approximately 10% and approximately 15%,approximately 10% and approximately 12%, approximately 12% andapproximately 15%, or between approximately 15% and approximately 20%antibacterial component by weight. In some embodiments, the amount ofantibacterial component by weight may be approximately 0.01%,approximately 0.05%, approximately 0.1%, approximately 0.5%,approximately 1%, approximately 1.5%, approximately 2%, approximately2.5%, approximately 3%, approximately 3.5%, approximately 4%,approximately 4.5%, approximately 5%, approximately 5.5%, approximately6%, approximately 6.5%, approximately 7%, approximately 7.5%,approximately 8%, approximately 8.5%, approximately 9%, approximately9.5%, approximately 10%, approximately 11%, approximately 12%,approximately 13%, approximately 14%, approximately 15%, approximately17%, approximately 19%, approximately 20%, or any other percentagebetween approximately 0.01% and 20% by weight of the topicalcomposition.

In various embodiments, the topical composition comprises anantimicrobial agent comprising an antifungal component comprising atleast two antifungal pharmaceutical drugs, an antibacterial componentcomprising at least two antibacterial pharmaceutical drugs, or anantifungal component comprising one or more antifungal pharmaceuticaldrugs and an antibacterial component comprising one or moreantibacterial pharmaceutical drugs.

In one example, the topical composition comprises one or more ofmupirocin, azithromycin, cefixime, nitrofurantoin, or tetracycline andan antifungal component selected from abafungin, albaconazole,amorolfin, amphotericin b, anidulafungin, bifonazole, butenafine,butoconazole, candicidin, caspofungin, ciclopirox, clotrimazole,econazole, fenticonazole, filipin, fluconazole, flucytosine,griseofulvin, haloprogin, hamycin, isavuconazole, isoconazole,itraconazole, ketoconazole, micafungin, miconazole, naftifine,natamycin, nystatin, omoconazole, oxiconazole, polygodial, posaconazole,ravuconazole, rimocidin, sertaconazole, sulconazole, terbinafine,terconazole, tioconazole, tolnaftate, undecylenic acid, voriconazole, ora combination thereof. The antifungal component may compriseitraconazole and/or fluconazole, for example. In one embodiment, thetopical composition comprises mupirocin and itraconazole, mupirocin andnystatin, cefixime and itraconazole or fluconazole, nitrofurantoin anditraconazole or fluconazole, nitrofurantoin and tetracycline and one orboth of itraconazole or fluconazole, or azithromycin and fluconazole. Inanother example, the topical composition comprises mupirocin and/orazithromycin and an additional antibacterial pharmaceutical drugidentified herein.

In another example, the topical composition comprises an antifungalcomponent including amphotericin b, ciclopirox, clotrimazole, econazole,fenticonazole, fluconazole, isoconazole, itraconazole, ketoconazole,naftifine, omoconazole, oxiconazole, polygodial, posaconazole,terbinafine, terconazole, tioconazole, tolnaftate, voriconazole, orcombination thereof and a second, different, antimicrobialpharmaceutical drug. For example, the topical composition may comprisean antibacterial component comprising the second antimicrobialpharmaceutical drug that includes one or more antibacterialpharmaceutical drugs selected from afenide, amikacin, amoxicillin,ampicillin, arsphenamine, azithromycin, azlocillin, aztreonam,bacampicillin, bacitracin, carbacephem (loracarbef), carbenicillin,cefaclor, cefadroxil, cefalotin, cefamandole, cefazolin, cefdinir,cefditoren, cefepime, cefixime, cefoperazone, cefotaxime, cefoxitin,cefpodoxime, cefprozil, ceftazidime, ceftibuten, ceftizoxime,ceftobiprole, ceftriaxone, cefuroxime, cephalexin, chloramphenicol,chlorhexidine, ciprofloxacin, clarithromycin, clavulanic acid,clindamycin, cloxacillin, colimycin, colistimethate teicoplanin,colistin, demeclocycline, dicloxacillin, dirithromycin, doripenem,doxycycline, efprozil, enoxacin, ertapenem, erythromycin, ethambutol,flucloxacillin, fosfomycin, furazolidone, gatifloxacin, geldanamycin,gentamicin, grepafloxacin, herbimycin, imipenem, isoniazid, kanamycin,levofloxacin, lincomycin, linezolid, lomefloxacin, meropenem,meticillin, metronidazole, mezlocillin, minocycline, mitomycin,moxifloxacin, mupirocin, nafcillin, neomycin, netilmicin,nitrofurantoin, norfloxacin, ofloxacin, oxacillin, oxytetracycline,paromomycin, penicillin G, penicillin V, piperacillin, pivmecillinam,platensimycin, polymyxin B, prontosil, pvampicillin, pyrazinamide,quinupristin/dalfopristin, rifampicin, rifampin, roxithromycin,sparfloxacin, spectinomycin, spiramycin, sulbactam, sulfacetamide,sulfamethizole, sulfamethoxazole, sulfanilimide, sulfisoxazole,sulphonamides, sultamicillin, telithromycin, tetracycline,thiamphenicol, ticarcillin, tobramycin, trimethoprim,trimethoprim-sulfamethoxazole, troleandomycin, trovafloxacin, or acombination thereof. In another example, the topical compositioncomprises an antifungal component including itraconazole and a second,different, antimicrobial pharmaceutical drug, comprising an additionalantifungal pharmaceutical drug selected from an azole. In one example,the azole includes clotrimazole, econazole, fluconazole, isoconazole,ketoconazole, voriconazole, or combination thereof. In another example,the additional antifungal pharmaceutical drug is selected fromantimetabolites, allylamines, morpholine, glucan synthesis inhibitors(echinocandins), polyenes, benoxaaborale; other antifungal/onychomycosisagents, and new classes of antifungal/onychomycosis agents. In anotherexample, the additional antifungal pharmaceutical drug is selected fromabafungin, albaconazole, amorolfin, anidulafungin, bifonazole,butenafine, butoconazole, candicidin, caspofungin, ciclopirox,fenticonazole, filipin, flucytosine, griseofulvin, haloprogin, hamycin,isavuconazole, micafungin, miconazole, naftifine, natamycin,omoconazole, oxiconazole, polygodial, posaconazole, ravuconazole,rimocidin, sertaconazole, sulconazole, terbinafine, terconazole,tioconazole, undecylenic acid, or a combination thereof. In anotherexample, the additional antifungal pharmaceutical drug is selected fromamphotericin b, nystatin, tolnaftate, or combination thereof.

In some examples, a topical composition comprises from approximately0.3% w/w to approximately 3% w/w, approximately 0.5% w/w toapproximately 2.5% w/w, approximately 1.0% w/w to approximately 9.0%w/w, approximately 2.0% w/w to approximately 8.0% w/w, fromapproximately 3.0% w/w to approximately 7.0% w/w, or from approximately4.0% w/w to approximately 7.0% w/w of an antifungal component identifiedherein. For example, the topical composition may comprise itraconazole,voriconazole, fluconazole, or combination thereof. In an example, thetopical composition comprises from approximately 0.3% w/w toapproximately 3% w/w, approximately 0.5% w/w to approximately 2.5% w/w,approximately 1.0% w/w to approximately 9.0% w/w, approximately 2.0% w/wto approximately 8.0% w/w, from approximately 3.0% w/w to approximately7.0% w/w, or from approximately 4.0% w/w to approximately 7.0% w/w of afirst antifungal drug identified herein and from approximately 0.3% w/wto approximately 3% w/w, approximately 0.5% w/w to approximately 2.5%w/w, approximately 1.0% w/w to approximately 9.0% w/w, approximately2.0% w/w to approximately 8.0% w/w, approximately 3.0% w/w toapproximately 7.0% w/w, or from approximately 4.0% w/w to approximately7.0% w/w of a second antifungal drug identified herein.

In various embodiments, the antimicrobial agent comprises anantibacterial agent selected from one or more antibacterials comprisingdoxycycline, ceftriaxone, cefixime, colistimethate, tobramycin,cefepime, gentamicin, streptomycin, sulfamethoxazole /trimethoprim,tetracycline, or nitrofurantoin. The topical composition may include atwo or more antibacterial drugs. For example, in some embodiments, thetopical composition comprises cefixime and an additional antibacterialpharmaceutical drug identified herein. In another example, the topicalcomposition comprises tetracycline and/or nitrofurantoin and anadditional antibacterial pharmaceutical drug identified herein.

In one example, the topical composition comprises from approximately0.3% w/w to approximately 3% w/w, approximately 0.5% w/w toapproximately 2.5% w/w, approximately 1.0% w/w to approximately 9.0%w/w, approximately 2.0% w/w to approximately 8.0% w/w, approximately3.0% w/w to approximately 7.0% w/w, or from approximately 4.0% w/w toapproximately 7.0% w/w of an antibacterial component identified herein.In another example, the topical composition comprises from approximately0.3% w/w to approximately 3% w/w, approximately 0.5% w/w toapproximately 2.5% w/w, approximately 1.0% w/w to approximately 9.0%w/w, approximately 2.0% w/w to approximately 8.0% w/w, approximately3.0% w/w to approximately 7.0% w/w, or from approximately 4.0% w/w toapproximately 7.0% w/w of a first antibacterial drug identified hereinand from approximately 0.3% w/w to approximately 3% w/w, approximately0.5% w/w to approximately 2.5% w/w, approximately 1.0% w/w toapproximately 9.0% w/w, approximately 2.0% w/w to approximately 8.0%w/w, approximately 3.0% w/w to approximately 7.0% w/w, or fromapproximately 4.0% w/w to approximately 7.0% w/w of a secondantibacterial drug identified herein. For example, the topicalcomposition may comprise mupirocin and tobramycin, mupirocin anddoxycycline, mupirocin and doxycycline hyclate, mupirocin andazithromycin, or mupirocin, doxycycline, and ketoconazole,nitrofurantoin and tetracycline, or cefixime and mupirocin ordoxycycline.

In one example, a topical composition comprises from approximately 0.3%w/w to approximately 3% w/w, approximately 0.5% w/w to approximately2.5% w/w, approximately 1.0% w/w to approximately 9.0% w/w,approximately 2.0% w/w to approximately 8.0% w/w, approximately 3.0% w/wto approximately 7.0% w/w, or from approximately 4.0% w/w toapproximately 7.0% w/w of an antifungal component identified herein andfrom approximately 0.3% w/w to approximately 3% w/w, approximately 0.5%w/w to approximately 2.5% w/w, approximately 1.0% w/w to approximately9.0% w/w, approximately 2.0% w/w to approximately 8.0% w/w,approximately 3.0% w/w to approximately 7.0% w/w, or from approximately4.0% w/w to approximately 7.0% w/w of an antibacterial componentidentified herein. For example, the antibacterial component may comprisenitrofurantoin, tetracycline, cefixime, doxycycline, tobramycin,ciprofloxacin, mupirocin, or combination thereof and the antifungalcomponent may comprise ketoconazole, itraconazole, voriconazole, orcombination thereof.

In some embodiments, the topical composition may comprise one or moreexcipients or additives. In an aspect, excipients or additives include,but are not limited to, the following: solvents, surfactants,humectants, preservatives, flavorings, stabilizers (includingantioxidants), binders, and colorants.

In various embodiments, the topical composition comprises theantibacterial component alone or in combination with one or moreadditional active agents selected from an antifungal component, anantiviral agent, an anti-inflammatory agent, an non-steroidalanti-inflammatory (NSAID) agent, an anti-allergic agent, anantimicrobial agent, an anti-depressant agent, a stimulant agent, adisinfectant agent, an anticonvulsant agent, a mucolytic agent, a localanesthetic agent, or combinations thereof, which may include one or moreactive pharmaceutical drugs of selected agents. In one embodiment, thetopical composition includes additional active agents selected from oneor more anticonvulsants, nerve depressants, muscle relaxants, NMDA(N-Methyl-D-aspartate) receptor antagonists, opiate or opioid agonists,antidepressants, and/or other active agents. In some embodiments, thetopical composition may comprise the antibacterial component alone or incombination with an antifungal component, steroid agent, antiviralcomponent, NSAID agent, antidepressant agent, anticonvulsant agent,analgesic agent, opioid agent, keratolytic agent, or combinationthereof, which may include one or more active pharmaceutical drugs ofselected components or agents. In various embodiments, the topicalcomposition may comprise the antibacterial component alone or incombination with one or more antifungal components.

As introduced above, the topical composition may comprise one or moreadditional active agents. It will be appreciated that topicalcompositions herein may include or specifically exclude additionalactive agents. It will also be appreciated that topical compositions mayexclude an antimicrobial agent and rather include one or more of theadditional active agents described herein.

In various embodiments, the topical composition comprises theantimicrobial agent and a nonsteroidal anti-inflammatory drug (NSAID)agent. The NSAID agent may include one or more NSAIDS selected fromoxicams, such as meloxicam or piroxicam; salicylic acid derivatives,such as aspirin, diflunisal, salsalate, or trilisate; propionic acids,such as flurbiprofen, ibuprofen, ketoprofen, naproxen, or oxaprozin;acetic acids, such as diclofenac, etodolac, indomethacin, ketorolac,nabumetone, sulindac, or tolmetin; fenamates, such as meclofenamate;and/or COX-2 inhibitors, such as celecoxib, rofecoxib, or valdecoxib. Invarious embodiments, the topical composition comprises betweenapproximately 0.01% and approximately 20% by weight NSAID agent. In anembodiment, the antimicrobial agent comprises cefixime, nitrofurantoin,tetracycline, or combination thereof. Additional antimicrobial agentsmay also be included. The topical composition may be formulated as asolution, which may include a suspension/dispersion, for nasalirrigation, nebulization to the upper or lower respiratory tract, ear,bath, spray, gauze, or irrigation of a foot, limb, torso, or wound, naillacquer, mouth gargle, or mouth wash. The topical composition may beformulated into a cream, lotion, ointment, gel, shampoo, or lozenge fortopical application to skin or mucosal tissue as described herein.

In some embodiments, the topical composition comprises the antimicrobialagent and a local anesthetic agent. The local anesthetic agent may beselected from lidocaine, prilocaine, benzocaine, or combination thereof.The local anesthetic agent may comprise between approximately 0.01% andapproximately 15% by weight of the topical composition. In anembodiment, the antimicrobial agent comprises cefixime, nitrofurantoin,tetracycline, or combination thereof. Additional antimicrobial agentsmay also be included. The topical composition may be formulated as asolution, which may include a suspension/dispersion, for nasalirrigation, nebulization to the upper or lower respiratory tract, ear,bath, spray, gauze, or irrigation of a foot, limb, torso, or wound, naillacquer, mouth gargle, or mouth wash. The topical composition may beformulated as cream, lotion, ointment, gel, shampoo, or lozenge fortopical application to skin or mucosal tissue as described herein.

In an embodiment, the topical composition comprises the antimicrobialagent a steroid agent. In one example, the steroid agent comprises acorticosteroid selected from amcinonide, betamethasone dipropionate,betamethasone valerate, clobetasol propionate, desoximetasone,diflorasone diacetate, flurandrenolide, fluticasone propionate,fluocinonide, halcinonide, halobetasol propionate, mometasone furoate,triamcinolone acetonide, or combination thereof. In various embodiments,the topical composition comprises between approximately 0.001% andapproximately 1% by weight steroid agent. In an embodiment, theantimicrobial agent comprises cefixime, nitrofurantoin, tetracycline, orcombination thereof. Additional antimicrobial agents may also beincluded. The topical composition may be formulated as a solution, whichmay include a suspension/dispersion, for nasal irrigation, nebulizationto the upper or lower respiratory tract, ear, bath, spray, gauze, orirrigation of a foot, limb, torso, or wound, nail lacquer, mouth gargle,or mouth wash. The topical composition may be formulated into a cream,lotion, ointment, gel, shampoo, or lozenge for topical application toskin or mucosal tissue as described herein.

In various embodiments, the topical composition comprises theantimicrobial agent and a muscle relaxant agent comprising one or moremuscle relaxants selected from baclofen, carisoprodol, chlorzoxazone,cyclobenzaprine, dantrolene, diazepam, metaxalone, methocarbamol,orphenadrine, quinine sulfate, tizanidine, and/or other musclerelaxants. In various embodiments, the topical composition comprisesbetween approximately 0.001% and approximately 5% by weight musclerelaxant agent. In an embodiment, the antimicrobial agent comprisescefixime, nitrofurantoin, tetracycline, or combination thereof.Additional antimicrobial agents may also be included. The topicalcomposition may be formulated as a solution, which may include asuspension/dispersion, for nasal irrigation, nebulization to the upperor lower respiratory tract, ear, bath, spray, gauze, or irrigation of afoot, limb, torso, or wound, nail lacquer, mouth gargle, or mouth wash.The topical composition may be formulated into a cream, lotion,ointment, gel, shampoo, or lozenge for topical application to skin ormucosal tissue as described herein.

In some embodiments, the topical composition comprises the antimicrobialagent and an anticonvulsant or nerve depressant agent. Theanticonvulsant or nerve depressant agent may comprise one or more nervedepressants and/or anticonvulsants selected from gabapentin, topiramate,lamotrigine, or combinations thereof. In various embodiments, theanticonvulsant or nerve depressant agent may comprise betweenapproximately 0.01% and approximately 20% by weight of the topicalcomposition. In an embodiment, the antimicrobial agent comprisescefixime, nitrofurantoin, tetracycline, or combination thereof.Additional antimicrobial agents may also be included. The topicalcomposition may be formulated as a solution, which may include asuspension/dispersion, for nasal irrigation, nebulization to the upperor lower respiratory tract, ear, bath, spray, gauze, or irrigation of afoot, limb, torso, or wound, nail lacquer, mouth gargle, or mouth wash.The topical composition may be formulated into a cream, lotion,ointment, gel, shampoo, or lozenge for topical application to skin ormucosal tissue as described herein.

In one embodiment, the topical composition comprises the antimicrobialagent and a NMDA receptor antagonist agent such as ketamine. In someembodiments, the topical composition may comprise an opiate or opioidagonist agent selected from tramadol; one or more C2 opiate agonistsselected from oxycodone, morphine, methadone, hydromorphone, andfentanyl; one or more C3 opiate agonists selected from hydrocodone,codeine, propoxyphene, butalbital, and pentazocine; or any combinationthereof. In an embodiment, the antimicrobial agent comprises cefixime,nitrofurantoin, tetracycline, or combination thereof. Additionalantimicrobial agents may also be included. The topical composition maybe formulated as a solution, which may include a suspension/dispersion,for nasal irrigation, nebulization to the upper or lower respiratorytract, ear, bath, spray, gauze, or irrigation of a foot, limb, torso, orwound, nail lacquer, mouth gargle, or mouth wash. The topicalcomposition may be formulated into a cream, lotion, ointment, gel,shampoo, or lozenge for topical application to skin or mucosal tissue asdescribed herein.

In an embodiment, the topical composition comprises the antimicrobialagent a keratolytic agent selected form urea, salicylic acid, papain, orcombinations thereof. For example, the topical composition may comprisethe antimicrobial agent and urea. In various embodiments, the topicalcomposition may comprise between approximately 1% and approximately 30%by weight urea. In an embodiment, the antimicrobial agent comprisescefixime, nitrofurantoin, tetracycline, or combination thereof.Additional antimicrobial agents may also be included. The topicalcomposition may be formulated as a solution, which may include asuspension/dispersion, for irrigation of a foot, limb, torso, or wound,or nail lacquer. The topical composition may be formulated into a cream,lotion, ointment, gel, or shampoo for topical application to skin ormucosal tissue as described herein.

In an embodiment, the topical composition comprises an antibacterialcomponent comprising cefixime, tetracycline, nitrofurantoin, orcombinations thereof alone or in combination with one or more additionalactive agents selected from an antifungal component, an antiviral agent,an anti-inflammatory agent, an non-steroidal anti-inflammatory (NSAID)agent, an anti-allergic agent, an antimicrobial agent, ananti-depressant agent, a stimulant agent, a disinfectant agent, ananticonvulsant agent, a mucolytic agent, a local anesthetic agent, orcombinations thereof, which may include one or more activepharmaceutical drugs of selected agents. In one example, the topicalcomposition includes additional active agents selected from one or moreanticonvulsants, nerve depressants, muscle relaxants, NMDA(N-Methyl-D-aspartate) receptor antagonists, opiate or opioid agonists,antidepressants, and/or other active agents. In one example, the topicalcomposition may comprise the antibacterial component alone or incombination with an antifungal component, steroid agent, antiviralcomponent, NSAID agent, antidepressant agent, anticonvulsant agent,analgesic agent, opioid agent, keratolytic agent, or combinationthereof, which may include one or more active pharmaceutical drugs ofselected components or agents. In various embodiments, the topicalcomposition may comprise the antibacterial component alone or incombination with one or more antifungal components identified herein.

The topical composition may be provided in a topical format, which mayinclude a carrier for topical administration. In various embodiments,the topical composition may include a colloid or emulsion (o/w, w/o),cream, lotion, ointment, foam, aqueous or non-aqueous gel, aqueous ornon-aqueous solution, which may include a suspension/dispersion, powder,nail lacquer, bath, or paste. The topical composition, for example, maycomprise an antibacterial component comprising cefixime, tetracycline,nitrofurantoin, or combinations thereof alone or in combination with oneor more additional active agents provided in an above topical format.

The topical composition may be administered topically by contacting anexternal surface of the body, which may include skin, e.g., intact,wounded, broken skin; nails; mucosal tissue lining a vaginal or analorifice. The topical composition may be administered topical bycontacting mucosal surfaces of vulva, vagina, anus, nose, mouth, ear,pharynx, upper respiratory tract, or lungs. The topical composition maybe administered in a spray, coating, soak, powder, spread, lozenge,chewable, rinse, or the like, for example, suitable to the topicalformat. The topical composition, for example, may comprise anantibacterial component comprising cefixime, tetracycline,nitrofurantoin, or combinations thereof alone or in combination with oneor more additional active agents provided in an above topical format.

The topical composition may comprise a solution, which may comprise asuspension/dispersion; cream; an oil; a gel; an ointment; a lozenge; ora gum as also described herein. The topical composition, for example,may comprise an antibacterial component comprising cefixime,tetracycline, nitrofurantoin, or combinations thereof alone or incombination with one or more additional active agents provided in anabove dosage form. Such dosage forms including the microbial agent maybe delivered, for example, by application, dissolution, or irrigation ata body cavity or orifice or topically to skin or a mucosal surface,e.g., drops applied to tear ducts or a mouth rinse, wash, or garglecomposition. In one example, the topical composition may be topicallyadministered to infected skin forming the outer body covering of asubject or to mucosal tissue of the vagina, oral cavity, respiratorytract, lungs, ear canal, or anus to treat a microbial infection. Forexample, the topical composition may comprise a solution orsuspension/dispersion for topical administration in an ear, hand, foot,mouth using a bath or irrigation. In another example, the topicalcomposition comprises a nail lacquer for administration to nails. Insome embodiments, the topical composition may be utilized as a woundtreatment and administered to broken or unbroken skin or mucosal tissueas indicated above and elsewhere herein.

In various embodiments, the topical composition may compriseantimicrobial agent and/or antifungal agent as disclosed herein in asolution for nasal irrigation, e.g., via Neil-Med® Irrigation Delivery;medium particle size nasal delivery, e.g., via NasoNeb® Nasal Nebulizer;small particle size nasal delivery, e.g., via PARI SinuStar™; smallparticle size lung (respiratory) delivery, e.g., via Omron® or PARInebulizers; ear delivery; topical bath irrigation; topical sprayapplication; topical irrigation application; topical gauze application;or other topical external application. The topical composition, forexample, may comprise an antibacterial component comprising cefixime,tetracycline, nitrofurantoin, or combinations thereof alone or incombination with one or more additional active agents provided in anabove topical format for topical delivery to lungs, nasal cavity,throat, upper or lower respiratory tract, ear, skin, mucosal tissue,limbs, torso, or body orifice.

In various embodiments, the topical composition is formulated forsuppository administration at a body orifice, such as the rectum,vagina, or urethra. In some embodiments, the composition may comprise adosage form including a capsule, tablet, gum, lozenge, or pouchconfigured for sublingual or sub-labial administration. The bodycavities or orifices may comprise one or more of the nasal cavity,nostrils, tear duct, anus, vagina, urethra, mouth, and ear canal.

The topical composition may be provided in an oral rinse solution ororal lozenge. The oral rinse may comprise a mouthwash. Oraladministration may also include application or an ointment, lotion,cream, or gel.

In some embodiments, the topical composition comprises a nail lacquerfor direct application to nail tissue. A nail lacquer format may includeone or more antimicrobial actives formulated for topical application tonail tissue. In some embodiments, a nail lacquer format may includeadditives such as thickening agents, plasticizers, polymers, volatileorganic compounds, or other additives to promote effective localizationof the medication following application. In some embodiments, a naillacquer format may comprise a solution. Solution is intended toencompass solvent and solute combinations wherein the solute isdissolved, suspended, dispersed, and/or mixed in the solute unlessstated otherwise. In some embodiments, a nail lacquer format may lacktraditional lacquer additives. In various embodiments, a nail lacquerformat may comprise an aqueous solution formulated for application to anail surface whereon the carrier evaporates or is absorbed. In someembodiments, a nail lacquer solution may have a fluid or semi-fluidconsistency. In some embodiments, a carrier for a nail lacquer formatmay be thickened with a viscosity agent to increase viscosity foradministration. In some embodiments, a nail lacquer format may comprisea solution comprising a cream, lotion, gel, or ointment.

Further to the above, in some embodiments, the topical compositioncomprises a treatment solution for a footbath, irrigation, or sprayadministration. In one example, the topical composition comprises atreatment solution for nasal or intranasal administration via irrigationor nebulization. In one example, the topical composition comprises atreatment solution for administration to an ear in a spray or drop. Inone example, the topical composition comprises a treatment solution foradministration to a mouth and comprises a drop, spit-rinse, mouthwash,or gargle format. In some embodiments, the topical composition may beadministered to the mouth and comprises a lozenge, chewable, ointment,cream, lotion, or gel format.

Methods of Making a Topical Composition

In various embodiments, a method of formulating the topical compositioncomprises combining the active agents including the antimicrobial agentand a topical carrier. For example, the method may include combining anantifungal and/or antibacterial component and a carrier. In one example,the antimicrobial agent comprises an antibacterial component comprisingcefixime, tetracycline, nitrofurantoin, or combinations thereof alone orin combination with one or more additional active agents describedherein. Cefixime may be combined with a carrier and additional actives,if present, in an amount between approximately 100 mg and approximately500 mg per dosage volume. Nitrofurantoin may be combined with a carrierand additional actives, if present, in an amount between approximately25 mg and approximately 300 mg, such approximately 200 mg or less.

The carrier may include one or more vehicles/carriers. The carrier maybe liquid, semi-liquid, or solid. For example, the carrier may includean aqueous, organic, or inorganic solution, which may include asuspension/dispersion, cream, gel, ointment, lotion, emulsion, powder,or paste. In some embodiments, the carrier includes a carrier or vehiclecomposition such as a base cream, ointment, gel, lotion, foam, orsolution. The carrier may include carriers such as lecithin,phospholipids, glycols, paraffin, fatty acids, carbopols/carbomers,alcohols, lanolin, for example.

In some embodiments, the carrier comprises an aqueous or non-aqueoussolution. In some examples, a carrier comprising an aqueous solution maybe combined with the antimicrobial agent to formulate a topicalcomposition comprising an irrigation solution, bath (e.g., footbath,soak), nail lacquer, drops, or topical spray, e.g., aerosol ornebulized, for example. In an embodiment, the carrier may include anaqueous solution comprising a saline solution. For example, the topicalcomposition may comprise a carrier comprising a sodium chloridesolution, which may be a sterile solution, an alcohol, dilute sodiumhypochlorite, hydrogen peroxide, Dakin's solution, water, e.g., purifiedwater, water for irrigation, water for injection, or a sterile water. Inone embodiment, a carrier comprises a sodium chloride 0.9% solution,which may be a sterile sodium chloride 0.9% solution. The carrier maycomprise an alcohol. The carrier may be present in an amount sufficientto obtain the desired amount of active agents per unit weight or volume.

The topical composition may include a carrier component comprising apolyethylene glycol (PEG) carrier component. In other embodiments, thecomposition is PEG-free. In these or other embodiments, the compositionmay include a silicon or silicon variant carrier component. In someembodiments, the composition is silicon-free. An example topicalcomposition may comprise a solution including carrier componentsselected from water, alcohol, DMSO, saline or sodium chloride, hydrogenperoxide, sodium hypochlorite, or other aqueous or non-aqueous carriermedium into which the one or more active agents are mixed, suspended,dispersed, solubilized, or dissolved. The topical composition may bewater soluble/miscible or formulated for water absorption. The topicalcomposition may comprise a water-in-oil emulsion or oil-in-wateremulsion. In one embodiment, the topical composition comprises anemulsion, e.g., a cream or lotion format, comprising one or more carriercomponents selected from of acrylate copolymer, alcohol, camphor,carbomer, dimethyl isosorbide, disodium EDTA, dl-alphatocopherylacetate, edetate disodium, emulsifying wax, eucalyptus oil, flavonoids,glycerin, glycol dicaprylate/dicaprate, hydroxyethyl cellulose,isopropyl myristate, lactic acid, meadowsweet extract, menthol, mineraloil, neopentyl, phenolic glycosides, polyethylene glycol (PEG),polysorbate (e.g., polysorbate 85, polysorbate 20), purified water,titanium dioxide, tridecyl stearate, tridecyl trimellitate, sodiumhydroxide, sodium hydroxide, sorbitol, stearic acid, zinc pyrithione, orcombinations thereof. In some embodiments, the topical compositioncomprises a foam format that includes propellant carrier component suchas butane. Topical compositions comprising a foam format may alsocomprise additional characteristics such as that of an emulsion, such asan oil-in-water emulsion, or gel.

In one example, the topical composition comprises an ointment format andincludes active agents in a carrier comprising carrier componentsselected from hydrophilic petrolatum, white petrolatum, hydrophilicointment, white ointment, anhydrous lanolin, hydrous lanolin,polyethylene glycol (PEG) ointment, or combinations thereof. In anembodiment, the topical composition comprises a gel format. The gel maybe an aqueous or non-aqueous gel. The gel may include carrier componentssuch as thickening agents and/or gelling agents such as carbopol,poloxamer, xanthan gum, methylcellulose, carboxymethyl cellulose,hydroxyethyl cellulose, ethylcellulose, gelatin, magnesium aluminumsilicate, polyvinyl alcohol, sodium alginate, or combinations thereof.The topical composition may include a powder format and include carriercomponents such as lactose or talc, for example.

The topical composition or carrier thereof may include carriercomponents such as one or more solubilizers, stabilizers, buffers,tonicity modifiers, bulking agents, viscosity enhancers/reducers,surfactants, chelating agents, binders, humectants, preservatives,flavorings, colorants, adjuvants, or combinations thereof.

In various embodiments, the topical composition or carrier thereofcomprises one or more glucose polymers such as a starch, cellulose,polydextrose, or combination thereof. Example starches may includesodium starch glycolate, corn starch, pregelatinized starch, orcombination thereof. Example celluloses may include hydroxypropylcellulose, hypromellose, croscarmellose sodium, ethyl cellulose,microcrystalline cellulose, or combination thereof. Povidone such aspovidone K30, copovidone, crospovidone, or combination thereof, may alsobe present. In some embodiments, glycol and/or a sugar alcohol may bepresent. Example glycols may include polyethylene glycol, propyleneglycol, or combination thereof. Example sugar alcohols may includemannitol. Some embodiments may include oxides such as silicon dioxide,titanium dioxide, ferric oxide, or combination thereof. One embodimentmay include any of the above and magnesium stearate, talc, diethylphthalate, sodium stearyl fumarate, sodium lauryl sulfate, polysorbate,triacetin, polacrilin, lactose, glycerol behenate, polyvinyl alcohol,carnauba wax, or combination thereof. In one embodiment, the topicalcomposition does not include one or more of starch, cellulose,polydextrose, sodium starch glycolate, corn starch, pregelatinizedstarch, hydroxypropyl cellulose, hypermellose, croscarmellose sodium,ethyl cellulose, microcrystalline cellulose, povidone, povidone K30,copovidone, crospovidone, polyethylene glycol, propylene glycol,mannitol, silicon dioxide, titanium dioxide, ferric oxide, magnesiumstearate, talc, diethyl phthalate, sodium stearyl fumarate, sodiumlauryl sulfate, polysorbate, triacetin, polacrilin, lactose, glycerolbehenate, polyvinyl alcohol, carnauba wax, or combination thereof.

As introduced above, the method may include combining the carrier and apowder containing all or a portion of the antimicrobial agent. Forexample, antifungal component comprising one or more antifungal activesand/or antibacterial component comprising one or more antibacterialactives may be obtained from bulk powder or powder for injection andcombined with the carrier. In one of an above or another example, one ormore actives of the antimicrobial agent may be obtained from one or morecommercially available oral capsules or tablets. Oral capsules may beopened to release contained powder or solubilized for combination withthe carrier. The oral tablets may be crushed and the resulting powdermay be combined with the carrier.

In addition to antimicrobial active drug, in various embodiments, powderfrom a capsule or crushed antimicrobial tablet may include excipients.For example, antimicrobial tablets may include one or more of a glucosepolymer, starch, and/or cellulose and one or more additional componentssuch as magnesium stearate, povidone, lactose, glycol, oxide, talc,triacetin, or an alcohol. In some embodiments, the resulting powderincludes a cellulose such as microcrystalline cellulose and one or moreof magnesium stearate, anhydrous dibasic calcium phosphate, or povidone.In one example, the powder may further include croscarmellose sodium. Ina further example, the powder may also include an oxide such as silicondioxide, ferric oxide, aluminum oxide, or combination thereof; a starch,such as sodium starch glycolate, corn starch, or both; sodium laurylsulfate, lactose, talc, or combinations thereof. In some embodiments,wherein the tablet includes a film coating, the method may includeremoval of all or a portion of a film coating.

When the method includes addition of crushed oral tablets, less than allthe powder of a crushed tablet may be used when the tablet contains moreactive drug than required. More than one crushed tablet may be used whenthe method includes formulating a topical composition comprising moreactive drug than is present in a single tablet. Similarly, the methodmay include addition of less than all powder of a capsule or multiplecapsules.

In an embodiment, powder obtained from a crushed antimicrobial drugtablet may be added to a carrier for compounding, such as a base forcompounding, or a commercially available medicated composition.

Tablets may include film coatings. For example, film coatings maycomprise polymer coatings such as a shellac. In some embodiments, themethod of formulating the topical composition may include removing allor a portion of such a film coating. In one example, the method includesremoval of all or a portion of the film coating prior to crushing thetablet. For example, the film coating may be removed by contacting theskin/coating with a solvent. The solvent may include an alcohol, sterilesodium chloride, or aqueous solvent such as water. Contacting mayinclude spraying or pouring the solvent onto the tablet to coat thetablet with the solvent. In one method, contacting includes submergingthe tablet in an excess of solvent. The contacted tablet may be shakenwith the solvent or may be allowed to rest for a sufficient period oftime for solvent to act. According to one method, the contacting may bebrief such as less than a minute, less than approximately 30 seconds,less than approximately 20 seconds, or between approximately 5 secondsand approximately 20 seconds. In one example, tablets coated in solventmay be quickly washed to remove the film coating after the solvent hascontacted the film coating for a suitable period of time. In anothermethod, a tablet including a film coating may be crushed and thereaftermixed with water or solvent, the powder including the film coating maythen go into solution. According to a version of the method, the powderand water or solvent may be shaken to accelerate the powder going intosolution.

A method of formulating the topical composition may include combiningone or more active agents, such as an antimicrobial agent as describedherein, and a carrier. In some embodiments, the antimicrobial agent mayinclude bulk powder formats of one or more antibacterial and/orantifungal drugs alone or in combination with the carrier. In someembodiments, bulk powder format may be in addition to powder fromcapsules, crushed tablets and/or powder for injection. Bulk powder maybe referred to in the art as pure powder. In some embodiments, powderfor injection may be in addition to powder from capsules, crushedtablets, and/or bulk powder. Combining may include adding all or aportion of the powder to be combined with all or a portion of thecarrier and mixing. In some embodiments, all or a portion of the powdermay be dispersed, suspended, or dissolved in a liquid to form a paste,or solution, which may include a suspension/dispersion, prior toaddition to the carrier. Capsules may be opened to release powder foraddition to the carrier directly or wetted or in solution. Capsules maybe dissolved or solubilized in the carrier or in a carrier component. Inone of an above or another embodiment, all or a portion of the powdermay be directly added to all or a portion of the carrier. According tovarious embodiments, the carrier may comprise a suitable carrierselected to formulate a topical composition comprising a format selectedfrom a cream, gel, lotion, ointment, emulsion (oil-in-water orwater-in-oil), foam, solution, dispersion, or powder, for example,suitable for topical application. The carrier may be present in anamount sufficient to obtain the desired amount of active agents per unitweight or volume. The one or more active agents may be mixed dispersed,suspended, solubilized, and/or dissolved with the carrier.

In some embodiments, the method includes formulating a carrier and/orcombining the active agents, including the antimicrobial agent, with acarrier comprising a base cream, ointment, gel, lotion, foam solution,or powder. The carrier may include lecithin, phospholipids, glycols,paraffin, fatty acids, carbopols/carbomers, alcohols, lanolin, orcombination thereof, for example. In one embodiment, the carriercomprises a sodium chloride 0.9% solution, which may be a sterile sodiumchloride 0.9% solution. Some embodiments may include polyethylene glycol(PEG), while other embodiments may be PEG-free. In an above embodimentor another embodiment, the carrier may include a silicon or siliconvariant or may be silicon-free. A carrier solution may comprise anaqueous or non-aqueous solution. Example solutions may include water,alcohol, DMSO, saline or sodium chloride, and/or sodium hypochlorite. Insome embodiments, the carrier comprises an aqueous solution such as asaline solution. For example, the topical composition may comprise acarrier comprising sodium chloride solution, which may be a sterilesolution, an alcohol, water, e.g., purified water, water for irrigation,water for injection, or a sterile water. The carrier may be watersoluble/miscible or formulated for water absorption, such as a gel.

In some embodiments, the method includes combining the active agents,including the antimicrobial agent, with a carrier to formulate a topicalcomposition comprising a water-in-oil emulsion or oil-in-water emulsion.For example, the carrier may comprise an emulsion having a cream orlotion format including one or more of acrylate copolymers, alcohol,camphor, carbomer, dimethyl isosorbide, disodium EDTA,dl-alphatocopheryl acetate, edetate disodium, emulsifying wax,eucalyptus oil, flavonoids, glycerin, glycol dicaprylate/dicaprate,hydroxyethyl cellulose, isopropyl myristate, lactic acid, meadowsweetextract, menthol, mineral oil, neopentyl, phenolic glycosides,polyethylene glycol (PEG), polysorbate (e.g., polysorbate 85,polysorbate 20), purified water, titanium dioxide, tridecyl stearate,tridecyl trimellitate, sodium hydroxide, sorbitol, stearic acid, zincpyrithione, or combinations thereof.

In some embodiments, the method includes combining the active agents,including the antimicrobial agent, with a carrier to formulate a topicalcomposition comprising an ointment format. For example, the carrier maycomprise hydrophilic petrolatum, white petrolatum, hydrophilic ointment,white ointment, anhydrous lanolin, hydrous lanolin, PEG ointment, orcombinations thereof. In some embodiments, the method includes combiningthe active agent with a carrier to formulate a topical compositioncomprising a gel. The gel may be an aqueous or non-aqueous gel. The gelmay include thickening agents and/or gelling agents such as carbopol,poloxamer, xanthan gum, methylcellulose, carboxymethyl cellulose,hydroxyethyl cellulose, ethylcellulose, gelatin, magnesium aluminumsilicate, polyvinyl alcohol, sodium alginate, or combinations thereof.In some embodiments, the method includes combining the active agent witha carrier to formulate a topical composition comprising a powder. Apowder carrier may include lactose or talc, for example. In someembodiments, the method may include imparting the carrier or topicalcomposition formulated therewith with a gas or pressurized propellant togenerate a foam format. For example, a propellant such as butane may beused to generate a foam from the carrier or combined carrier and activeagent. In various embodiments, the method may include utilizing acarrier or further combining of one or more carrier component additivessuch as solubilizers, stabilizers (which may include antioxidants),buffers, tonicity modifiers, bulking agents, viscosityenhancers/reducers, surfactants, chelating agents, adjuvants,humectants, preservatives, flavorings, binders, colorants, orcombinations thereof.

Further to the above, in some embodiments, the method includes combiningthe active agents, including the antimicrobial agent, with acommercially available carrier or base vehicle composition forcompounding. The carrier may be liquid, semi-liquid, or solid. Forexample, the carrier may include an aqueous, organic, or inorganicsolution, which may include a suspension/dispersion; cream; gel;ointment; lotion; emulsion; powder; or paste. Thus, the method offormulating the topical composition may include addition of crushedantimicrobial tablets or powder thereof to a topical base forcompounding to formulate creams, ointments, solutions/irrigations/baths,powders, gels, lotions, or pastes, for example. Non-limiting examplesmay include Spira-Wash® Gel, Lipoderm®, LoxaSperse®, XyliFos®, Mucolox™,or Versabase® Cream, Goam, Gel, Lotion or Shampoo, manufactured anddistributed by PCCA, 9901 South Wilcrest Drive, Houston, Tex. 77099.LoxaSperse® refers to an excipient base powder comprising a blend ofmicronized xylitol and poloxamers. LoxaSperse® is used as a chemicaldispersing or solubilizing agent, thereby improving the solubility anddispersibility of poorly water-soluble active pharmaceutical ingredients(APIs) or agents. LoxaSperse® can be obtained from a bulk source.XyliFos® refers to an excipient base powder comprising xylitol,poloxamer 407, hydroxypropyl betadex, and epigallocatechin gallate.XyliFos® is used as a chemical dispersing or solubilizing agent, therebyimproving the solubility and dispersibility of poorly water-solubleactive pharmaceutical ingredients (APIs) or agents. In an aspect,infectious agents such as bacteria and fungi can consume or uptakeXyliFos®, but cannot digest, process, or excrete XyliFos®. This leads tothe infectious agent's death. XyliFos® can be obtained from a bulksource.

In one embodiment, formulating the topical composition comprisescombining all or a portion of the active agents, including theantimicrobial agent, and a carrier comprising a commercially availablemedicated composition. In one example, the method includes combining allor a portion of an antimicrobial agent comprising one or more capsulesand/or crushed antimicrobial tablets and commercially availablemedicated composition. The commercially available medicated compositionmay comprise a cream, ointment, lotion, suspension/dispersion, solution,irrigation, bath, powder, gel, foam, or paste, for example. Thus, amethod of formulating the topical composition may comprise adding afirst portion of the active agent comprising bulk powder or crushedtablets to a medicated composition comprising a second portion of theactive agent and at least a portion of the carrier. In anotherembodiment, a method of formulating the topical composition may compriseadding a commercially available medicated composition comprising all ora portion of the antimicrobial agent or other active agent with acarrier. The commercially available medicated composition may comprise amedicated composition for oral administration, topical administration,ophthalmic administration, otic administration, nasal administration,transdermal administration, sublingual administration, or pulmonaryadministration.

In an embodiment, the method includes combining capsules or crushedtablets of a portion of the antimicrobial agent to another portion ofthe antimicrobial agent comprising another format, such as acommercially available medicated suspension, solution, ointment, cream,gel, lotion, or powder. In some such embodiments, the carrier may beprovided by the commercially available medicated composition. In variousembodiments, all or a portion of the antimicrobial agent may be added toone or more components of the carrier. Thereafter, additional carriercomponents and the remainder of the antimicrobial agent may be added toformulate the topical composition. Other active agents may also be addedbefore, after, or with the antimicrobial agent.

It will be appreciated that unless indicated otherwise, combining oradding active agents to the carrier or components thereof may includecombining or adding the active agents together or separately. In oneexample, combining the active agent and carrier results in a formulationof a topical composition having a different format than that of thecarrier, such a commercially manufactured base for compounding orcommercially manufactured medicated composition. Examples may includeaddition of additional carrier components such described above such asthickening agents, thinners, surfactants, carbomers, PEG, hydrocarbons,and/or diluents.

In various embodiments, the antimicrobial agent or portion thereofcomprises a commercially available medicated composition comprising acream, ointment, solution, powder, ground tablet, or gel and the carriercomprises a cream, ointment, lotion, liquid, gel, or paste base. In someembodiments, the method includes combining a first portion of theantimicrobial agent with a second portion of the antimicrobial agent,wherein the first portion comprises a commercially available medicatedcream, ointment, solution, powder, e.g., bulk powder, powder forinjection, capsule, or ground tablet, or a gel and the second portioncomprises a commercially available medicated cream, ointment, solution,powder, e.g., bulk powder, powder for injection, or ground tablet, or agel. The method may include combining the first and second portions andthe carrier together or separately. Is some examples, the carrier may beprovided by the combination of the commercially available medicatedcompositions. The antimicrobial agent may be one or more antifungalcomponents, one or more antibacterial components, or a combinationthereof.

In an example, the antimicrobial agent includes an antifungal componentcomprising itraconazole and the method of formulating the topicalcomposition comprises combining a carrier and a commercially availableitraconazole, such as Itraconazole Capsule; Itraconazole InjectionSolution; or bulk powder. In one example, the antimicrobial agentcomprises an antifungal component comprising itraconazole and the methodof formulating the topical composition comprises addition of a crusheditraconazole tablet to a carrier. The itraconazole tablets may comprisecommercially available itraconazole 200 mg oral tablets, for example.Itraconazole oral tablets may include colloidal silicon dioxide,crospovidone, hydrogenated vegetable oil, hypromellose, lactose,microcrystalline cellulose, magnesium stearate, propylene glycol, talc,and titanium dioxide, for example. The oral tablets may be crushed andcombined with the carrier to formulate a topical comprising betweenapproximately 0.01% and approximately 20% by weight, approximately 0.05%and approximately 2%, approximately 0.1% and approximately 2%,approximately 0.5% and approximately 2%, approximately 1% andapproximately 2%, or approximately 0.05%, approximately 0.1%,approximately 0.5%, approximately 2% and approximately 7%, approximately1%, approximately 2%, approximately 3%, approximately 4%, approximately5%, less than approximately 5%, or greater than approximately 10%itraconazole by weight. To formulate a topical composition comprising adesired percent by weight itraconazole, the total desired weight of thetopical composition is subtracted from the weight of crushed oralitraconazole tablet powder needed to obtain the desired percent byweight itraconazole in a manner similar to that described below withrespect to voriconazole.

In some embodiments, the antifungal component or a carrier comprising atleast a portion of the antifungal component may comprise a commerciallyavailable Itraconazole Oral Solution. For example, Itraconazole OralSolution may contain 10 mg of itraconazole per mL, solubilized byhydroxypropyl-β-cyclodextrin (400 mg/mL) as a molecular inclusioncomplex and may have a target pH of 2. Accordingly, the solution mayhave a low pH of approximately 2. Other ingredients may includehydrochloric acid, propylene glycol, purified water, sodium hydroxide,sodium saccharin, sorbitol, cherry flavor, and caramel flavor. It willbe appreciated that oral solutions comprising other flavorings may alsobe used if they become available. Similarly, other pH adjusting agentsmay also be used if they become available.

The topical composition comprising itraconazole may include a suitablecarrier selected to formulate a topical composition comprising a formatselected from a cream, gel, lotion, ointment, emulsion (oil-in-water orwater-in-oil), foam, solution, dispersion, or powder, for example,suitable for topical application. In an above or another example, thecarrier comprises a commercially available composition comprising abase, such as those described herein. In an above or another example,the carrier may comprise a commercially available medicated composition,such as those described herein. Further to the above, in some methods,carrier components described herein for formulating the formatsidentified above or elsewhere herein may also be added in addition to orinstead of a base composition or additional medicated compositionscomprising an ointment, cream, powder, solution, paste, gel, or otherformat. Additional active agents may include one or more antifungalactives, antibacterial actives, or both. Such additional antifungalcomponent may be present in a combined amount between approximately0.01% and approximately 20% by weight, such as between approximately0.01% and approximately 5%, approximately 0.01% and approximately 2% byweight, approximately 0.05% and approximately 2%, approximately 0.1% andapproximately 2%, approximately 0.5% and approximately 2%, approximately1% and approximately 2%, approximately 2% and approximately 7%, orapproximately 0.05%, approximately 0.1%, approximately 0.5%,approximately 1%, approximately 2%, approximately 3%, approximately 4%,approximately 5%, less than approximately 5%, or greater thanapproximately 10% by weight. For example, the method of formulating thetopical composition may comprise combining an antifungal componentincluding itraconazole and a second, different, antimicrobialpharmaceutical drug. For example, the method may include combiningitraconazole, e.g., itraconazole oral solution, and an antibacterialcomponent comprising the second antimicrobial pharmaceutical drugselected from afenide, amikacin, amoxicillin, ampicillin, arsphenamine,azithromycin, azlocillin, aztreonam, bacampicillin, bacitracin,carbacephem (loracarbef), carbenicillin, cefaclor, cefadroxil,cefalotin, cefamandole, cefazolin, cefdinir, cefditoren, cefepime,cefixime, cefoperazone, cefotaxime, cefoxitin, cefpodoxime, cefprozil,ceftazidime, ceftibuten, ceftizoxime, ceftobiprole, ceftriaxone,cefuroxime, cephalexin, chloramphenicol, chlorhexidine, ciprofloxacin,clarithromycin, clavulanic acid, clindamycin, cloxacillin, colimycin,colistimethate teicoplanin, colistin, demeclocycline, dicloxacillin,dirithromycin, doripenem, doxycycline, efprozil, enoxacin, ertapenem,erythromycin, ethambutol, flucloxacillin, fosfomycin, furazolidone,gatifloxacin, geldanamycin, gentamicin, grepafloxacin, herbimycin,imipenem, isoniazid, kanamycin, levofloxacin, lincomycin, linezolid,lomefloxacin, meropenem, meticillin, metronidazole, mezlocillin,minocycline, mitomycin, moxifloxacin, mupirocin, nafcillin, neomycin,netilmicin, nitrofurantoin, norfloxacin, ofloxacin, oxacillin,oxytetracycline, paromomycin, penicillin G, penicillin V, piperacillin,pivmecillinam, platensimycin, polymyxin B, prontosil, pvampicillin,pyrazinamide, quinupristin/dalfopristin, rifampicin, rifampin,roxithromycin, sparfloxacin, spectinomycin, spiramycin, sulbactam,sulfacetamide, sulfamethizole, sulfamethoxazole, sulfanilimide,sulfisoxazole, sulphonamides, sultamicillin, telithromycin,tetracycline, thiamphenicol, ticarcillin, tobramycin, trimethoprim,trimethoprim-sulfamethoxazole, troleandomycin, trovafloxacin, or acombination thereof. In some embodiments, the method includes combiningthe itraconazole, e.g., itraconazole oral solution or ground tablets,with a medicated composition comprising the antibacterial drug. Suchmedicated compositions may include ointment, gel, cream, powder (crushedtablets), paste, lotion, or solution formats, for example. Someembodiments may include combining a medicated antibacterial compositionselected from one or more of the medicated antibacterial compositionsdescribed herein. In another example, the topical composition comprisesan antifungal component including itraconazole and a second, different,antimicrobial pharmaceutical drug, comprising an additional antifungalpharmaceutical drug selected from an azole. In one example, the azoleincludes clotrimazole, econazole, fluconazole, isoconazole,ketoconazole, voriconazole, or combination thereof. In another example,the additional antifungal pharmaceutical drug is selected fromantimetabolites, allylamines, morpholine, glucan synthesis inhibitors(echinocandins), polyenes, benoxaaborale, other antifungal/onychomycosisagents, and new classes of antifungal/onychomycosis agents. In anotherexample, the additional antifungal pharmaceutical drug is selected fromabafungin, albaconazole, amorolfin, anidulafungin, bifonazole,butenafine, butoconazole, candicidin, caspofungin, ciclopirox,fenticonazole, filipin, flucytosine, griseofulvin, haloprogin, hamycin,isavuconazole, micafungin, miconazole, naftifine, natamycin,omoconazole, oxiconazole, polygodial, posaconazole, ravuconazole,rimocidin, sertaconazole, sulconazole, terbinafine, terconazole,tioconazole, undecylenic acid, or a combination thereof. In anotherexample, the additional antifungal pharmaceutical drug is selected fromamphotericin b, nystatin, tolnaftate, or combination thereof. In someembodiments, the method includes combining the itraconazole, e.g.,itraconazole oral solution or ground tablets, with a medicatedcomposition comprising the additional antifungal drug. Such medicatedcompositions may include ointment, gel, cream, powder (crushed tablets),paste, lotion, or solution formats, for example. Some embodiments mayinclude combining a medicated antifungal composition comprising theadditional antifungal pharmaceutical drug selected from one or more ofthe medicated antifungal compositions described herein.

Additionally or alternatively, additional actives may include otheractive agents such as one or more active agents selected from anantiviral agent, an anti-inflammatory agent, a steroid, an anti-allergicagent, an antidepressant agent, a stimulant agent, a disinfectant agent,an anticonvulsant agent, a local anesthetic agent, an anticonvulsantagent, a nerve depressant agent, a muscle relaxant agent, a NMDA(N-Methyl-D-aspartate) receptor antagonist agent, an opiate or opioidagonist agent, an NSAID agent, an analgesic agent, a keratolytic agent,or combination thereof. Such additional active agents may be present ina combined amount between approximately 0.01% and approximately 25% byweight, such as between approximately 1% and approximately 10%. In oneexample, the method may include combining crushed itraconazole tabletsand/or itraconazole oral solution and a medicated ointment, cream,solution, lotion, or powder comprising one or more additional antifungalpharmaceutical drugs or one or more antibacterial drugs consistent withthe present disclosure.

The topical composition comprising itraconazole may be utilized as partof a treatment of a microbial infection. In one example, the topicalcomposition may be topically administered to infected skin forming theouter body covering of a subject or to mucosal tissue of the vagina oranus to treat a microbial infection. For example, the topicalcomposition may comprise a solution or suspension/dispersion for topicaladministration in a hand or footbath or by irrigation. In anotherexample, the topical composition comprises a nail lacquer foradministration to nails. In some embodiments, the topical compositionmay be utilized as a wound treatment and administered to broken orunbroken skin or mucosal tissue as indicated above and elsewhere herein.

In an example, the antimicrobial agent includes an antifungal componentcomprising amphotericin and the method of formulating the topicalcomposition comprises combining a carrier and a commercially availableamphotericin, such as Amphotericin B injection, Lipid Complex;Amphotericin B Injection, Powder, Lyophilized, for Solution; or bulkpowder.

In an example, the antimicrobial agent includes an antifungal componentcomprising econazole and the method of formulating the topicalcomposition comprises combining a carrier and a commercially availableeconazole such as an Econazole Nitrate cream. Some methods may includecombining bulk powders. In an above or another example, the methodincludes combining Econazole Nitrate 1.0% Cream or Econazole NitrateFoam.

In an example, the antimicrobial agent includes an antifungal componentcomprising fluconazole and the method of formulating the topicalcomposition comprises combining a carrier and commercially availablefluconazole, such as Fluconazole in Dextrose Injection Solution;Fluconazole in Sodium Chloride Injection, Solution; FluconazoleInjection; Fluconazole Powder, for Suspension; Fluconazole Tablets; orbulk powder. In another example, the method of formulating the topicalcomposition comprises addition of a crushed fluconazole tablet to acarrier. Less than all the powder of a crushed tablet may be used whenthe tablet contains more fluconazole than required. More than onecrushed tablet may be used when the method includes formulating atopical composition comprising more fluconazole than is in the tablet.The fluconazole tablet may comprise a commercially available fluconazole100 mg or 200 mg oral tablet. In some embodiments, other strengthtablets may be used. In addition to fluconazole, the powder may includea glucose polymer and one or more additional components such asmagnesium stearate, povidone, lactose, glycol, oxide, talc, triacetin,or an alcohol. In some embodiments, the powder includes a cellulose suchas microcrystalline cellulose and one or more of magnesium stearate,anhydrous dibasic calcium phosphate, or povidone. In one example, thepowder may further include croscarmellose sodium. In a further example,the powder may also include an oxide such as silicon dioxide, ferricoxide, aluminum oxide, or combination thereof; a starch, such as sodiumstarch glycolate, corn starch, or both; sodium lauryl sulfate, lactose,and talc. In various embodiments, the method may comprise crushing oneor more fluconazole tablets into a powder for use in the method. Methodsmay include crushing 100 mg or 200 mg fluconazole tablets, for instance.In some embodiments, powder obtained from a crushed fluconazole tabletmay be mixed with components of a carrier composition and, thereafter,additional components may be added to formulate the topical compositionas described in more detail elsewhere herein. In an embodiment, powderobtained from the crushed tablet may be added to a carrier forcompounding, such as a base for compounding, or a commercially availablemedicated composition.

In an example, the antimicrobial agent includes an antifungal componentcomprising ketoconazole and the method of formulating the topicalcomposition comprises combining a carrier and commercially availableketoconazole, such as 50 mg, 100 mg, or 200 mg tablets. In an above oranother example, the method includes combining Ketoconazole Foam,Ketoconazole Cream, Ketoconazole Suspension, or Ketoconazole SuspensionShampoo.

In an example, the antimicrobial agent includes an antifungal componentcomprising nystatin and the method of formulating the topicalcomposition comprises combining a carrier and a commercially availablenystatin, such as Nystatin Powder (Topical), or bulk powder. In an aboveor another example, the method combining Nystatin Cream or NystatinOintment.

In one example, the antimicrobial agent includes an antifungal componentcomprising clotrimazole and the method of formulating the topicalcomposition comprises combining a carrier and a commercially availableclotrimazole such as a Clotrimazole Cream, Clotrimazole Lotion,Clotrimazole Liquid, or Clotrimazole Solution. In some formulations,bulk powder or crushed tablets may be used.

In an above or another example, the method includes combining anantifungal component with a carrier wherein the antifungal componentcomprises a commercially available voriconazole composition such asVoriconazole Ophthalmic Ointment or Voriconazole Oral Suspension. TheVoriconazole Oral Suspension may include 45 g powder for oral suspensionfor reconstitution with water to produce a suspension containing 40mg/mL voriconazole and including colloidal silicon dioxide, titaniumdioxide, xanthan gum, sodium citrate dihydrate, sodium benzoate,anhydrous citric acid, natural orange flavor, and sucrose. In oneexample, the antimicrobial agent comprises an antifungal componentcomprising voriconazole and a method of formulating the topicalcomposition comprises addition of a crushed voriconazole tablet to acarrier. The voriconazole tablets may comprise commercially availablevoriconazole 50 mg, 100 mg, 200 mg oral tablets. In some embodiments,other strength tablets may be used. In addition to voriconazole, thepowder may include a glucose polymer and one or more additionalcomponents such as magnesium stearate, povidone, lactose, glycol, oxide,talc, triacetin, or an alcohol. In one example, the powder includescroscarmellose sodium, lactose monohydrate, magnesium stearate, povidoneand pregelatinized starch. In a further example, the powder may includehypromellose, lactose monohydrate, polyethylene glycol, talc andtitanium dioxide. In another example, the powder may include a starchsuch as pregelatinized starch, a cellulose such as croscarmellose sodiumand/or hypromellose. The powder may also include one or more of lactosemonohydrate, magnesium stearate, povidone, titanium dioxide, ortriacetin. In another example, the powder may include a starch,croscarmellose sodium, lactose monohydrate, magnesium stearate,polyethylene glycol, polyvinyl alcohol, povidone, talc, and titaniumdioxide. In another example, the powder may further include talc. In oneexample, the powder includes lactose monohydrate, pregelatinized starch(corn), croscarmellose sodium, povidone, magnesium stearate and acoating containing polyvinyl alcohol-part hydrolyzed, titanium dioxide,macrogol/PEG and talc. In one embodiment, the powder may includepregelatinized starch, croscarmellose sodium, lactose monohydrate,magnesium stearate, povidone, and a coating containing hypromellose,lactose monohydrate, titanium dioxide and triacetin. In someembodiments, powder obtained from a crushed voriconazole tablet may bemixed with components of a carrier composition and, thereafter,additional components may be added to formulate the topical compositionas described in more detail elsewhere herein. In various embodiments,the method comprises combining an antimicrobial agent and a carrierwherein the antimicrobial agent comprises an antibacterial component.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising a vancomycin and the method of formulating thetopical composition comprises combining a carrier and commerciallyavailable vancomycin. In one example, the method includes combining avancomycin powder, such as Vancomycin Hydrochloride for Injection, USP,which is a lyophilized powder for preparing intravenous (IV) infusions.The powder may be provided in vials (e.g., bottles) containing theequivalent of 500 mg, 1 g, 5 grams, 10 grams vancomycin base. Somemethods may utilize Vancomycin Hydrochloride USP powder for oralsolution, equivalent to 3.75 g, 7.5 g or 15 g vancomycin, and diluent,which may be a flavored, e.g., grape-flavored, diluent forreconstitution; or Vancomycin Intravenous Solution, e.g., vancomycinhydrochloride 5 mg/mL, sodium chloride 9 mg/mL.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising ciprofloxacin and the method of formulating thetopical composition comprises combining a carrier and a commerciallyavailable ciprofloxacin, such Ciprofloxacin HydrochlorideSolution/Drops; Ciprofloxacin Hydrochloride Tablets; CiprofloxacinTablets, e.g., 500 mg or 100 mg; Ciprofloxacin Hydrochloride Suspension;Ciprofloxacin Injection, USP, e.g., Ciprofloxacin Injection, USP, 20 mL,200 mg, 1% and 40 mL or 400 mg, 1%, for intravenous injection andinfusion, Premix 100 mL in 5% Dextrose, 200 mg, 0.2% and 200 mL in 5%Dextrose or 400 mg, 0.2%, for intravenous infusion; or bulk powder. Inone example, the method of formulating the topical composition comprisesaddition of a crushed ciprofloxacin tablet to a carrier. Theciprofloxacin tablets may comprise commercially available ciprofloxacinhydrochloride 250 mg, 500 mg, or 750 mg oral tablets, for example. Insome embodiments, other strength tablets may be used. In addition tociprofloxacin the powder may include the powder may include a glucosepolymer and one or more additional components such as magnesiumstearate, povidone, lactose, glycol, oxide, talc, triacetin, or analcohol. In one example, the powder includes a starch such ascornstarch, sodium starch glycolate. The powder may also includemagnesium stearate and/or lactose. In one embodiment, the powderincludes a cellulose such as croscarmellose sodium and/ormicrocrystalline cellulose. The powder may also include magnesiumstearate, povidone, and/or and oxide such as silicone dioxide. In anembodiment, the powder includes a cellulose such as hypromellose and/ormicrocrystalline cellulose. The powder may also include a starch such ascornstarch and/or sodium starch glycolate. In a further example, thepowder also includes magnesium stearate. In still a further example, thepowder includes polydextrose, silicon dioxide, titanium dioxide, talc,and/or triacetin. The powder may also include polyethylene glycol. Inone embodiment, the powder includes a cellulose such as microcrystallinecellulose. The powder may also include a starch such as sodium starchglycolate. In some embodiments, the powder obtained from a crushedciprofloxacin tablet may be mixed with components of a base or carriercomposition and, thereafter, additional components may be added toformulate the topical composition. In an embodiment, powder obtainedfrom the crushed tablet may be added to a base or carrier forcompounding or a commercially available medicated composition asdescribed in more detail elsewhere herein. In various embodiments, themethod may comprise crushing one or more ciprofloxacin tablets into apowder. Methods may include crushing 250 mg, 500 mg, 750 mgciprofloxacin tablets, for instance. In some examples, other strengthtablets may be used.

In one example, the antimicrobial agent comprises an antibacterialcomponent comprising levofloxacin and a method of formulating thetopical composition comprises addition of a crushed levofloxacin tabletto a carrier. The levofloxacin tablets may comprise commerciallyavailable levofloxacin 250 mg, 500 mg, or 750 mg oral tablets, forexample. In some embodiments, other strength tablets may be used. Inaddition to levofloxacin, the powder may include a glucose polymercomprising a starch and/or a cellulose and one or more additionalcomponents such as magnesium stearate, povidone, lactose, glycol, oxide,talc, triacetin, an alcohol, or combination thereof. In one example, thepowder includes cornstarch, croscarmellose sodium, hypromellose,microcrystalline cellulose, magnesium stearate, polyethylene glycol,povidone and titanium dioxide. In another example, the powder includessodium starch glycolate, hypromellose, microcrystalline cellulose,magnesium stearate, polyethylene glycol, propylene glycol, povidone,polysorbate, colloidal silicon dioxide, and titanium dioxide. In stillanother example, the powder includes hypromellose, microcrystallinecellulose, magnesium stearate, polyethylene glycol 6000, crospovidone,talc and titanium dioxide. In yet another example, the powder includessodium starch glycolate, croscarmellose sodium, hydroxypropyl cellulose,hypromellose, polyethylene glycol 400, povidone K 30, glycerol behenate,lactose monohydrate, colloidal silicon dioxide, titanium dioxide, ferricoxide, and talc. In some embodiments, the powder obtained from a crushedlevofloxacin tablet may be mixed with components of a base or carriercomposition and, thereafter, additional components may be added toformulate the topical composition. In an embodiment, powder obtainedfrom the crushed tablet may be added to a base or carrier forcompounding or a commercially available medicated composition asdescribed in more detail elsewhere herein. In various embodiments, themethod may comprise crushing one or more levofloxacin tablets into apowder. Methods may include crushing 250 mg, 500 mg, 750 mg levofloxacintablets, for instance. In some examples, other strength tablets may beused.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising levofloxacin and the method of formulating thetopical composition comprises combining a carrier and a commerciallyavailable levofloxacin, such as Levofloxacin Injection, which may besupplied in single-use vials containing a concentrated solution with theequivalent of 500 mg of levofloxacin USP in 20 mL vials and 750 mg oflevofloxacin USP in 30 mL vials; Levofloxacin Solution/Drops;Levofloxacin Tablet 250 mg, 500 mg, 750 mg; or bulk powder.

Levofloxacin is commercially available in a bulk powder format as wellas in capsule, solution/drops, oral solution, and injection dosageformulations. Levofloxacin is currently administered orally in tabletand oral solution dosage forms. Levofloxacin tablets are commerciallyavailable in various strengths including in 200 mg, 500 mg, and 750 mgtablets. Levofloxacin oral solution is commercially available in theUnited States in 25 mg/mL strength formulations. Such oral solutionsalso include inactives such as vehicles, solvents, stabilizers, coloringagents, or flavoring agents. In one example, levofloxacin oral solutioncontains, in addition to levofloxacin, artificial and natural flavors,ascorbic acid, benzyl alcohol, caramel color, glycerin, hydrochloricacid, propylene glycol, purified water, sucralose and sucrose. Asanother example, levofloxacin oral solution contains the followinginactive ingredients: artificial bubble gum flavor, artificial grapeflavor, ascorbic acid, benzyl alcohol, glycerin, hydrochloric acid, PFCBitter Mask F9885, propylene glycol, purified water, saccharin sodium,and sucrose. Sodium hydroxide may be used to adjust pH (betweenapproximately 5.0 to approximately 6.0). Levofloxacin is also currentlyadministered parenterally via intravenous injection. Levofloxacin forinjection is commercially available in various strengths and volumes.For example, levofloxacin for injection is currently available in 500mg/20 mL strength, 20 mL volume single use container, and in 250 mg/50mL strength, 50 mL, 100 mL, and 150 mL single-use containers.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising azithromycin and the method of formulating thetopical composition comprises combining a carrier and a commerciallyavailable azithromycin, such as Azithromycin for Injection USP, whichmay be supplied in lyophilized form under a vacuum in a 10 mL vialequivalent to 500 mg of azithromycin for intravenous administrationincluding sodium hydroxide and 413.6 mg citric acid; Azithromycin forOral Suspension, USP, which may be supplied for suspension in 100 mg/5mL or 200 mg/5 mL; Azithromycin Tablets; or bulk powder.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising clindamycin and the method of formulating thetopical composition comprises combining a carrier and a commerciallyavailable clindamycin, such as Clindamycin Phosphate Cream; ClindamycinPhosphate Gel; Clindamycin Phosphate Suspension; Clindamycin PhosphateInjection Solution; Clindamycin Phosphate for Injection; or bulk powder.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising doxycycline and the method of formulating thetopical composition comprises combining a carrier and a commerciallyavailable doxycycline, such as Doxycycline Hyclate tablets; DoxycyclineHyclate Tablets; Doxycycline Hyclate Pellets; Doxycycline forSuspension; Doxycycline Hyclate Powder for Suspension; or bulk powder.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising mupirocin and the method of formulating the topicalcomposition comprises combining a carrier and a commercially availablemupirocin, such as Mupirocin Ointment; Mupirocin Cream; or bulk powder.Mupirocin Ointment may be a mupirocin 2.0% ointment wherein each gram ofointment contains 20 mg mupirocin in a bland water miscible ointmentbase (polyethylene glycol ointment, NF) comprising polyethylene glycol400 and polyethylene glycol 3350. Mupirocin Cream may include mupirocin2.0% cream USP containing 2.15% w/w mupirocin calcium USP (equivalent to2% mupirocin free acid) in an oil- and water-based emulsion supplied in15-gram and 30-gram tubes.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising cefepime and the method of formulating the topicalcomposition comprises combining a carrier and a commercially availablecefepime, such as Cefepime Hydrochloride Injection, Powder, forSolution, supplied in 500 mg, 1 g, and 2 g vials; Cefepime HydrochlorideInjection Solution; or bulk powder.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising ceftriaxone and the method of formulating thetopical composition comprises combining a carrier and commerciallyavailable ceftriaxone, such as Ceftriaxone for Injection Powder,Ceftriaxone for Injection Solution, or bulk powder. In addition toceftriaxone, the ceftriaxone powder may include sodium. Ceftriaxone forInjection Solution may include a dextrose diluent and pH modifiers suchas sodium hydroxide and/or hydrochloric acid to provide a pH in therange of 6.0 and 8.0. Ceftriaxone for Injection Solution may be providedcontainers including 1 g equivalent of ceftriaxone, iso-osmotic withapproximately 1.9 g Dextrose Hydrous, USP, added; 2 g equivalent ofceftriaxone, iso-osmotic with approximately 1.2 g Dextrose Hydrous, USP,added.

In example, the antimicrobial agent includes an antibacterial componentcomprising nitrofurantoin and a method of formulating the topicalcomposition comprises combining nitrofurantoin and a carrier. Additionalantimicrobial agent, other active agents, and/or excipients may also beused. Nitrofurantoin may include a commercially available nitrofurantoinformat or bulk powder. In one example, nitrofurantoin comprisescommercially available nitrofurantoin capsules. The nitrofurantoincapsules may comprise 25 mg, 50 mg, and 100 mg strength capsules. A 100mg nitrofurantoin capsule may include a hard gelatin capsule shellcontaining the equivalent of 100 mg of nitrofurantoin in the form of 25mg of nitrofurantoin macrocrystals and 75 mg of nitrofurantoinmonohydrate. The capsule may also contain carbomer 934P, corn starch,compressible sugar, D&C Yellow No. 10, edible gray ink, FD&C Blue No. 1,FD&C Red No. 40, gelatin, lactose, magnesium stearate, povidone, talc,and titanium dioxide. In another embodiment, nitrofurantoin capsules maycomprise 25 mg, 50 mg, and 100 mg strength capsules including 25 mg, 50mg, or 100 mg nitrofurantoin microcrystals. The capsule may includeedible black ink, gelatin, lactose, starch, talc, titanium dioxide, andmay contain FD&C Yellow No. 6 and D&C Yellow No. 10.

In some embodiments, the topical composition may be formulated toinclude nitrofurantoin oral suspension. Nitrofurantoin oral suspensionis available in 25 mg/5 mL liquid suspension for oral administration.Nitrofurantoin Oral Suspension USP may contain carboxymethylcellulosesodium, anhydrous citric acid, glycerin, magnesium aluminum silicate,methylparaben, natural and artificial flavor (peach), propylparaben,purified water, saccharin sodium, sodium citrate, and sorbitol solution.

In example, the antimicrobial agent includes an antibacterial componentcomprising tetracycline and a method of formulating the topicalcomposition comprises combining tetracycline and a carrier. Additionalantimicrobial agent, other active agents, and/or excipients may also beused. Tetracycline may include a commercially available tetracyclineformat or bulk powder. In one example, tetracycline comprisescommercially available tetracycline capsules. Capsules may include 250mg or 500 mg tetracycline hydrochloride and inactive ingredientsincluding lactose, magnesium stearate, and sodium lauryl sulfate orcolloidal silicon dioxide, pregelatinized starch and stearic acid.

In some embodiments, the topical composition is formulated withtetracycline ointment. Tetracycline ointment is available in 30 mg pergram strength and includes inactive ingredients acetic acid, ascorbicacid, chlorhexidine gluconate, cholecalciferol, dimethyl sulfoxide,dipropylene glycol, glucono delta lactone, glycerin, histidine,hydroxethylc-cellulose, magnesium stearate, methylparaben, sodiumhydroxide, sorbic acid, steric acid, water.

In example, the antimicrobial agent includes an antibacterial componentcomprising cefixime and a method of formulating the topical compositioncomprises combining cefixime and a carrier. Additional antimicrobialagent, other active agents, and/or excipients may also be used. Cefiximemay include a commercially available cefixime format or bulk powder. Inone example, cefixime comprises commercially available chewable tabletcontaining either 100 mg or 150 mg or 200 mg of cefixime as trihydrate.The tablet may additionally contain the following inactive ingredients:aspartame, colloidal silicon dioxide, crospovidone, low substitutedhydroxypropyl cellulose, magnesium stearate, mannitol, and flavoringsuch as fantasy flavor perm seal and tutti frutti flavor. In oneexample, cefixime comprises a commercial oral tablet, such as a 400 mgoral cefixime tablet USP including dibasic calcium phosphate,hypromellose, lactose monohydrate, magnesium stearate, microcrystallinecellulose, polyethylene glycol, pregelatinized starch, titanium dioxide,and triacetin. In another embodiment, the cefixime comprises acommercial capsule, such as a 400 mg cefixime capsule includingcolloidal silicon dioxide, crospovidone, low substituted hydroxy propylcellulose, magnesium stearate, and mannitol. The capsule shell maycontain ferric oxide black, ferric oxide red, gelatin, potassiumhydroxide, propylene glycol, shellac, sodium lauryl sulfate, andtitanium dioxide. In an example, the cefixime comprises commercialcefixime powder for oral suspension USP, 100 mg/5 mL, 200 mg/5 mL, and500 mg/5 mL, including the following inactive ingredients: colloidalsilicon dioxide, sodium benzoate, sucralose (in 500 mg/5 mL strength),sucrose, and xanthan gum. The powder may also include flavoring, such asstrawberry flavoring.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising streptomycin and the method of formulating thetopical composition comprises combining a carrier and a commerciallyavailable streptomycin, such as Streptomycin for Injection USP, whichmay be supplied in 1 g vials; Streptomycin Injection, Powder,Lyophilized, for Solution; or bulk powder.

In an example, the antimicrobial agent includes an antibacterialcomponent comprising sulfamethoxazole/trimethoprim and the method offormulating the topical composition comprises combining a carrier and acommercially available sulfamethoxazole/trimethoprim, such asSulfamethoxazole and Trimethoprim Tablets; Sulfamethoxazole andTrimethoprim Injection; Sulfamethoxazole and Trimethoprim Suspension; orbulk powder.

In an embodiment, the method of formulating the topical compositioncomprises combining a carrier and a commercially available AzithromycinOral Suspension, Ciprofloxacin Cream, Ciprofloxacin Ointment,Clindamycin Cream, Clindamycin Ointment, Clindamycin Gel, Gentamycindrops, Gentamycin Spray, Gentamycin Cream, Gentamycin Ointment,Levofloxacin Injection Solution, Levofloxacin Drops, Mupirocin Ointment,Mupirocin Cream, Tobramycin Ophthalmic Ointment, Tobramycin OphthalmicDrops, and/or Tobramycin Otic Drops.

In one example, the antimicrobial agent comprises an antibacterialcomponent comprising linezolid and a method of formulating the topicalcomposition comprises addition of a crushed linezolid tablet to acarrier. The linezolid tablets may comprise commercially availablelinezolid 600 mg oral tablets, for example. In some embodiments, otherstrength tablets may be used. In addition to linezolid the powder mayinclude a glucose polymer comprising a starch and/or a cellulose and oneor more additional components such as magnesium stearate, povidone,lactose, glycol, oxide, talc, triacetin, an alcohol, or combinationthereof. In various examples, the powder includes a starch and acellulose. In other embodiments, the powder does not include a starch.In one example, the powder includes croscarmellose sodium, diethylphthalate, ethyl cellulose, pregelatinized starch, sodium starchglycolate, mannitol, colloidal silicon dioxide, povidone, copovidone,cospovidine, sodium stearyl fumarate, hypromellose, polyethylene glycol,titanium dioxide, magnesium stearate, microcrystalline cellulose, talc,hydroxypropyl cellulose, polydextrose, triacetin, carnauba wax, lactosemonohydrate, polacrilin potassium, sodium lauryl sulfate, or acombination thereof. In one example, the powder includes a starchcomprising pregelatinized starch, a cellulose comprising hypromellose, asugar alcohol comprising mannitol, a glycol comprising polyethyleneglycol, an oxide comprising titanium dioxide and/or colloidal silicondioxide, a povidone comprising copovidone, and sodium stearyl fumarate.In another example, the powder includes a cellulose comprisingcroscarmellose sodium, ethyl cellulose, hypromellose, and/ormicrocrystalline cellulose, magnesium stearate, povidone, an oxidecomprising silicon dioxide and/or titanium dioxide, talc, and diethylphthalate. In yet another example, the powder comprises a cellulosecomprising microcrystalline cellulose, hydroxypropyl cellulose, and/orhypromellose, polydextrose, magnesium stearate, crospovidone,polyethylene glycol, titanium dioxide, and triacetin. In one embodiment,the powder comprises a starch selected from cornstarch and/or sodiumstarch glycolate, a cellulose comprising microcrystalline cellulose,hypromellose, and/or hydroxypropylcellulose, magnesium stearate,polyethylene glycol, titanium dioxide, and carnauba wax. In anotherexample, the powder comprises hypromellose, lactose monohydrate,magnesium stearate, polyethylene glycol, colloidal silicon dioxide,titanium dioxide, polacrilin potassium, and carnauba wax. In oneembodiment, the powder comprises a cellulose comprising croscarmellosesodium and/or hypromellose, lactose monohydrate, magnesium stearate,polyethylene glycol 400, povidone and titanium dioxide. In anotherembodiment, the powder comprises a cellulose comprising croscarmellosesodium and/or microcrystalline cellulose, polydextrose, magnesiumstearate, polyethylene glycol, sodium lauryl sulfate, colloidal silicondioxide, titanium dioxide and triacetin. In some embodiments, the powderobtained from a crushed linezolid tablet may be mixed with components ofa base or carrier composition and, thereafter, additional components maybe added to formulate the topical composition. In an embodiment, powderobtained from the crushed tablet may be added to a base or carrier forcompounding or a commercially available medicated composition asdescribed in more detail elsewhere herein.

Linezolid for oral suspension may be supplied as a flavored, e.g.,orange-flavored, granule/powder for constitution into a suspension fororal administration. Depending on the strength and constitution ratio,following constitution, each 5 mL typically contains approximately 100mg of linezolid. Inactive ingredients may include sucrose, citric acid,sodium citrate, microcrystalline cellulose and carboxymethylcellulosesodium, aspartame, xanthan gum, mannitol, sodium benzoate, colloidalsilicon dioxide, sodium chloride, and flavors. Sodium (Na+) content maybe approximately 8.52 mg per 5 mL (0.4 mEq per 5 mL). For example, Zyvoxoral suspension is a white fluid, which is orange flavored. It issupplied in an amber glass bottle with a screw cap. Zyvox oralsuspension may contain 20 mg of linezolid per 1 mL (total 150 mL),sucrose, mannitol, microcrystalline cellulose, carmellose sodium,aspartame, anhydrous colloidal silica, sodium citrate, xanthan gum,sodium benzoate, citric acid anhydrous, and sodium chloride. Thegranules may be flavored with Mafco magnasweet, orange flavor, orangecream flavor, Sweet-am powder, vanilla flavor and peppermint flavor.

Linezolid injection may be supplied as a ready-to-use sterile isotonicsolution for intravenous infusion. For example, each container maycontain 600 mg of linezolid in 300 mL of a clear, colorless to slightlyyellow aqueous solution. Inactive ingredients may include: citric acidanhydrous USP 1.92 mg/mL, sodium chloride USP 9 mg/mL, sodium hydroxideNF 0.76 mg/mL, and water for injection USP. Sodium hydroxide NF and/orhydrochloric acid NF are typically used to adjust the pH. The sodium(Na+) content may be approximately 3.98 mg/mL (52 mEq/300-mL container).Zyvox for injection is supplied as a ready-to-use sterile isotonicsolution for intravenous infusion. Each mL contains 2 mg of linezolid.Inactive ingredients are sodium citrate, citric acid, and dextrose in anaqueous vehicle for intravenous administration. The sodium (Na+) contentis approximately 0.38 mg/mL (5 mEq per 300-mL bag; 3.3 mEq per 200-mLbag; and 1.7 mEq per 100-mL bag).

In one embodiment, the method includes mixing linezolid oral suspensionwith a carrier component and/or one or more active agents, such as anantibacterial component or an antifungal component. An example, oralsuspension may include inactive ingredients such as sucrose, citricacid, sodium citrate, microcrystalline cellulose andcarboxymethylcellulose sodium, aspartame, xanthan gum, mannitol, sodiumbenzoate, colloidal silicon dioxide, sodium chloride, or combinationthereof.

In an embodiment, the topical composition comprises a treatment solutionfor a footbath comprising a commercially available clindamycin solutionand a carrier comprising a diluent, such as any diluent describedherein. In one example, the clindamycin solution comprises a 1%clindamycin solution. In another example, the treatment solutioncomprises approximately 30 mL or 60 mL 1% clindamycin solution with asuitable amount of diluent for the footbath.

In an embodiment, the topical composition comprises a treatment solutionfor a footbath comprising a commercially available erythromycin solutionand a carrier comprising a diluent, such as any diluent describedherein. In one example, the erythromycin solution comprises a 2%erythromycin solution. In another example, the treatment solutioncomprises approximately 30 mL or 60 mL 2% erythromycin solution with asuitable amount of diluent for the footbath.

In an embodiment, the topical composition comprises a treatment solutionincluding a pharmaceutically effective amount of the antibacterialcomponent levofloxacin and a carrier comprising a diluent, such as anysuitable diluent for topical administration. In various embodiments, thetreatment solution is compounded from commercially availablelevofloxacin bulk powder, ground levofloxacin tablets, levofloxacin oralsolution, levofloxacin for injection, or a combination thereof. In anaspect, a suitable diluent comprises one or more aqueous diluents. Inone aspect, all or a portion of the diluent may be selected from water,sodium chloride, saline, Dakin's solution, sodium hypochlorite, orcombination thereof. In one example, the diluent comprises sterile waterfor irrigation. In various embodiments, the treatment solution compriseslevofloxacin oral solution. For example, the treatment solution maycomprise commercially available oral solution of levofloxacin anddiluent, such as levofloxacin 125 mg/5 mL (25 mg/mL) solution. In afurther aspect, a method of treating a bacterial infection may includetopically administering the levofloxacin oral solution to an affectedexterior body region such as an outer body surface such as skin or tomucosal lining of the vagina or anus. The topical administration mayinclude a bathing administration, which may include submerging all or aportion of an affected body region or surface in the treatment solution,e.g., in a bath application, irrigating all or a portion of the affectedbody region or surface with the treatment solution in an irrigationapplication, or otherwise contacting all or a portion of the affectedbody region or surface with the treatment solution, such as by sprayingthe treatment solution onto all or a portion of the affected body regionor surface in a topical spray application.

In an aspect, a treatment solution may contain between approximately 1mg and approximately 2000 mg, such as between approximately 100 mg andapproximately 1000 mg, approximately 250 mg and approximately 750 mg,approximately 250 mg and approximately 500 mg, or approximately 750 mglevofloxacin in an administration volume. According to variousembodiments, an administration volume may be approximately 20 mL toapproximately 4 L, such as approximately 30 mL to approximately 2 L,approximately 40 mL to approximately 1.5 L, or approximately 40 mL toapproximately 1 L. Administration volumes greater than 4 L may also beused, e.g. greater than 5 L, greater than 10 L, greater than 15 L, orgreater than 20 L.

In an aspect, a treatment solution may include between approximately0.01 mg/mL and approximately 24 mg/mL levofloxacin, such asapproximately 0.5 mg/mL and approximately 2 mg/mL, approximately 1 mg/mLand approximately 10 mg/mL, approximately 5 mg/mL and approximately 13mg/mL, or approximately 10 mg/mL and approximately 20 mg/mL. In anaspect, the treatment solution may include greater than a 25 mg/mLlevofloxacin concentration.

In an aspect, a topical composition comprises a treatment solutionincluding a pharmaceutically effective amount of the antibacterialcomponent linezolid and a carrier comprising a diluent, such as anysuitable diluent for topical administration. In various embodiments, thetreatment solution is compounded from commercially available linezolidbulk powder, ground linezolid tablets, linezolid solution, linezolidsolution of injection or infusion, or a combination thereof. In anaspect, a suitable diluent comprises one or more aqueous diluents. Inone aspect, all or a portion of the diluent may be selected from water,sodium chloride, saline, Dakin's solution, sodium hypochlorite, orcombination thereof. In one example, the diluent comprises sterile waterfor irrigation. In various embodiments, the treatment solution comprisesall or a portion of a linezolid tablet dissolved, dispersed, orsuspended in diluent. For example, the treatment solution may comprisecommercially available linezolid tablets and diluent, such as linezolid600 mg tablets, whereby the linezolid tablets may have be ground into afine powder and combined with the diluent. In a further aspect, a methodof treating a bacterial infection may include topically administeringthe treatment solution to an affected exterior body region such as anouter body surface such as skin or to mucosal lining of the vaginalorifice or anus. The topical administration may include a bathingadministration, which may include submerging all or a portion of anaffected body region or surface in the treatment solution, e.g., in abath application, irrigating all or a portion of the affected bodyregion or surface with the treatment solution in an irrigationapplication, or otherwise contacting all or a portion of the affectedbody region or surface with the treatment solution, such as by sprayingthe treatment solution onto all or a portion of the affected body regionor surface in a spray application.

In an aspect, a treatment solution may contain between approximately 1mg and approximately 2000 mg, such as between approximately 100 mg andapproximately 1000 mg, approximately 150 mg and approximately 750 mg,approximately 200 mg and approximately 500 mg, such as approximately 200mg, approximately 250 mg, approximately 300 mg, approximately 350 mg,approximately 400 mg, approximately 500 mg, approximately 550 mg, orapproximately 600 mg linezolid in an administration volume. According tovarious embodiments, an administration volume may be betweenapproximately 20 mL and approximately 4 L, such as approximately 30 mLand approximately 2 L, approximately 40 mL and approximately 1.5 L, orapproximately 40 mL and approximately 1 L.

In an aspect, a treatment solution may include between approximately0.01 mg/mL and approximately 2 mg/mL linezolid, such as approximately0.075 mg/mL and approximately 1 mg/mL, approximately 0.1 andapproximately 0.5 mg/mL, approximately 0.1 and approximately 0.4 mg/mL,approximately 0.15 mg/mL and approximately 0.2 mg/mL, approximately0.075 mg/mL and approximately 0.15 mg/mL. In an aspect, the treatmentsolution may include greater than a 0.15 mg/mL linezolid concentration.

In one embodiment, the topical composition comprises a treatmentsolution including an antimicrobial agent including an antifungalcomponent comprising the antifungal component itraconazole and a carriercomprising a diluent, such as any suitable diluent for topicaladministration. In various embodiments, the treatment solution iscompounded from commercially available itraconazole bulk powder, grounditraconazole tablets, itraconazole oral solution, or a combinationthereof. In an aspect, a suitable diluent comprises one or more aqueousdiluents. In one aspect, all or a portion of the diluent may be selectedfrom water, sodium chloride, saline, Dakin's solution, sodiumhypochlorite, or combination thereof. In one example, the diluentcomprises sterile water for irrigation, sterile water, or water forinjection.

In one embodiment, the topical composition comprises a treatmentsolution comprising itraconazole oral solution. For example, thetreatment solution may comprise commercially available oral solution ofitraconazole and diluent, such as itraconazole 10 mg/mL solution, whichmay also contain hydrochloric acid, propylene glycol, purified water,sodium hydroxide, sodium saccharin, sorbitol, cherry flavor, and caramelflavor. In a further aspect, a method of treating a fungal infection,which may include preventing, may include topically administering theitraconazole oral solution to an affected exterior body region such asan outer body surface such as skin or to mucosal lining of the vaginalorifice or anus. In various embodiments, the itraconazole oral solutionmay be directly applied to skin or mucosal tissue. In some embodiments,a pH adjusting agent may be added to increase the pH, e.g., toapproximately 3 or less than approximately 3, approximately 4 or lessthan 4, approximately 5 or less than approximately 5, approximately 6 orless than approximately 6, or approximately 7 or less than approximately7. The topical administration may include a bathing administration,which may include submerging all or a portion of an affected body regionor surface in the itraconazole oral solution, e.g., in a bathapplication, irrigating all or a portion of the affected body region orsurface with the itraconazole oral solution in an irrigationapplication, or otherwise contacting all or a portion of the affectedbody region or surface with the itraconazole oral solution, such as byspraying the oral solution onto all or a portion of the affected bodyregion or surface in a topical spray application. In some examples, theskin or mucosal tissue may comprise a broken or intact tissue. In oneembodiment, itraconazole oral solution may be utilized as a naillacquer. Consistent with the present disclosure, some embodiments mayinclude additional antifungal actives, antibacterial actives, oradditional actives agents combined with the itraconazole oral solution.Similarly, some embodiments may include combining carrier or componentsthereof with the itraconazole oral solution.

In one embodiment, a method of formulating the topical compositioncomprises combining itraconazole oral solution with a carrier toformulate a treatment solution. For example, the method may comprisecombining itraconazole 10 mg/mL solution and a diluent. The diluent maybe any suitable diluent for topical administration. For example, thediluent may be an aqueous or non-aqueous diluent. In one example, asuitable diluent comprises one or more aqueous diluents. All or aportion of the diluent may be selected from water, sodium chloride,saline, hydrogen peroxide, Dakin's solution, sodium hypochlorite, orcombination thereof. In one example, the diluent comprises sterile waterfor irrigation, sterile water, or water for injection. In a furtheraspect, a method of treating a fungal infection, which may includepreventing, may include topically administering the topical compositionto an affected exterior body region such as an outer body surface suchas skin or to mucosal lining of the vagina or anus. The topicaladministration may include a bathing administration, which may includesubmerging all or a portion of an affected body region or surface in thetopical solution, e.g., in a bath application, irrigating all or aportion of the affected body region or surface with the topical solutionin an irrigation application, or otherwise contacting all or a portionof the affected body region or surface with the topical solution, suchas by spraying the topical solution onto all or a portion of theaffected body region or surface in a topical spray application. In someexamples, the skin or mucosal tissue may comprise a broken or intacttissue. In one embodiment, topical composition may comprise itraconazoleoral solution combined with a carrier to formulate a nail lacquercomposition as described herein. Consistent with the present disclosure,some embodiments may include additional antifungal actives,antibacterial actives, or additional actives agents combined with theitraconazole oral solution. Similarly, some embodiments may includecombining carrier or components thereof with the itraconazole oralsolution.

In an aspect, a treatment solution may contain between approximately 10mg and approximately 300 mg, such as between approximately 40 mg andapproximately 250 mg, approximately 50 mg and approximately 200 mg,approximately 50 mg and approximately 125 mg, approximately 150 mg andapproximately 200 mg itraconazole in an administration volume. In anaspect, a treatment solution for a small treatment area may containbetween approximately 1 mg and approximately 30 mg, such as betweenapproximately 5 mg and approximately 25 mg, approximately 10 mg andapproximately 25 mg, approximately 10 mg and approximately 25 mg,approximately 15 mg and approximately 20 mg itraconazole in anadministration volume.

In various embodiments, a method of formulating the topical compositionmay comprise combining itraconazole oral solution, 10 mg/mL, and adiluent, wherein the itraconazole oral solution is combined in an amountbetween approximately 1 mL and approximately 25 mL in an administrationvolume. For example, the amount of itraconazole oral solution in anadministration volume may be between approximately 1 mL andapproximately 3 mL, approximately 3 mL and approximately 25 mL,approximately 5 mL and approximately 20 mL, approximately 5 mL andapproximately 10 mL, approximately 10 mL and approximately 20 mL,approximately 15 mL and approximately 25 mL, or greater thanapproximately 1 mL, approximately 2 mL, approximately 5 mL,approximately 10 mL, approximately 15 mL, approximately 20 mL, or lessthan approximately 25 mL.

According to various embodiments, an administration volume may bebetween approximately 20 mL and approximately 4 L, such as approximately30 mL and approximately 2 L, approximately 40 mL and approximately 1.5L, or approximately 40 mL and approximately 1 L. Administration volumesgreater than 4 L may also be used, e.g. greater than 5 L, greater than10 L, greater than 15 L, or greater than 20 L. In some embodiments, anadministration volume for a small treatment area may comprise betweenapproximately 1 mL and approximately 5 mL, such as approximately 1 mLand approximately 4 mL, approximately 1 mL and approximately 3 mL,approximately 2 mL and approximately 5 mL, approximately 2 mL andapproximately 3 mL, or between approximately 3 mL and approximately 5mL.

In an aspect, a treatment solution may include between approximately0.01 mg/mL and approximately 9.5 mg/mL itraconazole, such as betweenapproximately 0.5 mg/mL and approximately 9 mg/mL, approximately 1 mg/mLand approximately 8 mg/mL, approximately 2 mg/mL and approximately 7mg/mL, or approximately 10 mg/mL and approximately 20 mg/mL. In anembodiment, the treatment solution may include greater than a 10 mg/mLitraconazole concentration.

In some embodiments, the method may comprise combining itraconazole,e.g., itraconazole oral solution, with a carrier formulate a topicalcomposition comprising a cream, lotion, gel, or paste. For example,itraconazole oral solution may be combined with a base cream, baselotion, base gel, base ointment, or base powder. In some embodiments,carrier components such as thickening or gelling agents may be combinedwith the itraconazole oral solution. Additional carrier components, suchas those described herein, may also be utilized to formulate a desiredconsistency, feel, penetration, coverage, dispersion, or the like. In afurther aspect, a method of treating a fungal infection, which mayinclude preventing, may include topically administering the topicalcomposition to an affected exterior body region such as an outer bodysurface such as skin or to mucosal lining of the vagina or anus. Thetopical composition may be contacted to all or a portion of the affectedbody region or surface, such as by covering or spreading the topicalcomposition onto all or a portion of the affected body region orsurface. In some examples, the skin or mucosal tissue may comprise abroken or intact tissue. Consistent with the present disclosure, someembodiments may include additional antifungal actives, antibacterialactives, or additional actives agents combined with the itraconazole,e.g., itraconazole oral solution. Similarly, some embodiments mayinclude combining a carrier, which may include multiple carriers, withthe itraconazole oral solution.

In various embodiments, the method of formulating the topicalcomposition comprises combining itraconazole oral solution and anadditional azole; itraconazole oral solution and an additionalantifungal active drug; itraconazole oral solution and an antibacterialcomponent comprising one or more antibacterial active drugs;itraconazole oral solution and an additional active agent according tothe methods identified below or elsewhere herein; or combinationthereof. In some examples, the method may include combining one or morecommercially available medicated compositions comprising one or moreadditional actives. The method may further include combining a carrieras described herein.

In various embodiments, nitrofurantoin may be combined with a carrier toformulate a solution for topical administration to skin, mucosal tissue,ear, respiratory tract, wound, limb, torso, mouth, or scalp for example.The nitrofurantoin may comprise nitrofurantoin bulk powder, capsules, ororal suspension, for example. In various embodiments, nitrofurantoinoral suspension may be used to formulate shampoos, bath solutions,irrigation solutions, creams, lotions, or gels, for example, for topicaladministration to skin, vaginal orifice, anus, scalp, limbs, torso,nails, or wounds. In one embodiment, oral suspension may be used toformulate a nebulization solution for deliver to the upper or lowerrespiratory tract.

In various embodiments, nitrofurantoin may be present in an amountbetween approximately 10 mg and approximately 500 mg, such as betweenapproximately 25 mg and approximately 400 mg or between approximately 50mg and approximately 100 mg, approximately 100 mg and approximately 150mg, approximately 150 mg and approximately 200 mg, approximately 200 mgand approximately 250 mg, approximately 250 mg and approximately 300 mg,approximately 300 mg and approximately 350 mg, approximately 350 mg andapproximately 400 mg.

In various embodiments, the topical composition comprises anantimicrobial agent comprising an antibacterial component includingcefixime and/or nitrofurantoin. A method of formulating the topicalcomposition may comprises combining a carrier and cefixime and/ornitrofurantoin. The cefixime and/or nitrofurantoin may comprise bulkpowder commercially available cefixime and/or nitrofurantoin, such ascefixime capsules, cefixime oral tablets, cefixime oral chewabletablets, cefixime powder for oral suspension, nitrofurantoin capsules,or nitrofurantoin oral suspension. In one example, the method mayutilize cefixime 100 mg, 200 mg, or 150 mg oral chewable tablets,cefixime 400 mg oral tablets, nitrofurantoin 25 mg, 50 mg, or 100 mgcapsules, or nitrofurantoin 25 mg/g oral suspension.

In an aspect, the topical composition may include between approximately0.01 mg/mL and approximately 400 mg/mL cefixime and/or nitrofurantoin,such as approximately 0.075 mg/mL and approximately 1 mg/mL,approximately 0.1 mg/mL and approximately 1 mg/mL, approximately 0.1 andapproximately 2 mg/mL, approximately 2 mg/mL and approximately 10 mg/mL,approximately 10 mg/mL and approximately 50 mg/mL, approximately 10mg/mL and approximately 100 mg/mL, approximately 50 mg/mL andapproximately 150 mg/mL, approximately 100 and approximately 200 mg/mL,approximately 200 mg/mL and approximately 300 mg/mL, and approximately300 mg/mL and approximately 400 mg/mL. In an aspect, the topicalcomposition may include greater than approximately 0.075 mg/mL,approximately 0.15 mg/mL, approximately 0.2 mg/mL, approximately 0.4mg/mL, approximately 0.5 mg/mL, approximately 1 mg/ mL, approximately 10mg/mL, approximately 20 mg/mL, approximately 30 mg/mL, approximately 50mg/mL, approximately 75 mg/mL, approximately 100 mg/mL, approximately200 mg/mL, approximately 250 mg/mL, approximately 300 mg/mL, orapproximately 400 mg/mL cefixime and/or nitrofurantoin.

In an aspect, an administration volume of the topical composition maycontain between approximately 100 mg and approximately 45000 mg, such asbetween approximately 200 mg and approximately 425 mg, approximately 150mg and approximately 425 mg, approximately 200 mg and approximately 400mg, such as approximately 100 mg, approximately 15000 mg, approximately200 mg, approximately 250 mg, approximately 300 mg, approximately 350mg, approximately 375 mg, approximately 400 mg, approximately 410 mg,approximately 425 mg, or approximately 400 mg cefixime. The topicalcomposition may be administered 1 to 2 times daily. A daily dosage maycomprise between approximately 200 mg and approximately 800 mg cefixime,or between approximately 400 mg and approximately 700 mg cefiximeprovided in 1 to 2 administration volumes. In some instances, dailydosages may be administered in more than 2 administrations.

In an aspect, an administration volume of the topical composition maycontain between approximately 10 mg and approximately 250 mg, such asbetween approximately 25 mg and approximately 200 mg, approximately 50mg and approximately 200 mg, or approximately 100 mg and approximately200 mg, such as approximately 25 mg, approximately 50 mg, approximately75 mg, approximately 100 mg, approximately 125 mg, approximately 150 mg,approximately 175 mg, approximately 200 mg, or approximately 225 mgnitrofurantoin. A daily dosage may comprise between approximately 50 mgand approximately 600 mg nitrofurantoin, or between approximately 100 mgand approximately 400 mg nitrofurantoin provided in 1 to 2administrations, e.g., in 1 to 2 administration volumes.

According to various embodiments, the topical composition comprising atreatment solution including cefixime and/or nitrofurantoin in a spray,bath, or irrigation format may include an administration volume betweenapproximately 20 mL and approximately 4 L, such as approximately 30 mLand approximately 2 L, approximately 40 mL and approximately 1.5 L, orapproximately 40 mL and approximately 1 L. A treatment solution for abathing administration may include an administration volume betweenapproximately 500 mL and approximately 10 L, approximately 1 L andapproximately 8 L, approximately 1 L and approximately 4 L, orapproximately 3 L and approximately 8 L, as examples.

Topical composition comprising cefixime and/or nitrofurantoin maycomprise cream, lotion, paste, ointment, or similar format applied bycontact to skin, or mucosal tissue with respect to anal or vaginaladministration. In some embodiments, the topical composition may beformulated in a shampoo carrier for administration in a shampoo. In someformats, the composition may be administered to an infected or targetarea via spray, drops, wash, swab, sponge, absorbent dressing, coating(e.g., a nail lacquer), soaking, submerging, footbath, instillation orirrigation. Embodiments comprising a nail lacquer formulation may beapplied directly to nails, to treat a bacterial or fungal nailinfection.

In some embodiments, the method may comprise combining cefixime and/ornitrofurantoin with a carrier to formulate a topical compositioncomprising a cream, lotion, gel, or paste. For example, cefixime and/ornitrofurantoin powder, e.g., from a capsule or ground tablet, orsuspension may be combined with a base cream, base lotion, base gel,base ointment, or base powder. In some embodiments, carrier componentssuch as thickening or gelling agents may be combined with the powder orsuspension. Additional carrier components, such as those describedherein, may also be utilized to formulate a desired consistency, feel,penetration, coverage, dispersion, or the like. In a further aspect, amethod of treating a bacterial infection, which may include preventing,may include topically administering the topical composition comprisingcefixime and/or nitrofurantoin to an affected exterior body region suchas an outer body surface such as skin or to mucosal lining of the vaginaor anus, or oral cavity. The topical composition may be contacted to allor a portion of the affected body region or surface, such as by coveringor spreading the topical composition onto all or a portion of theaffected body region or surface. In some examples, the skin or mucosaltissue may comprise a broken or intact tissue. Consistent with thepresent disclosure, some embodiments may include additionalantibacterial actives, antifungal actives, or additional actives agentscombined with the cefixime and/or nitrofurantoin. Similarly, someembodiments may include combining a carrier, which may include multiplecarriers, with the cefixime and/or nitrofurantoin.

The topical composition comprising cefixime and/or nitrofurantoin may beutilized as part of a treatment of a microbial infection. The topicalcomposition comprising cefixime and/or nitrofurantoin may be utilized ina treatment methodology to treat or prevent a bacterial infection. Thebacterial infection may be a Gram-negative and/or Gram-positivebacteria, which may include MDRO organisms or strains thereof, such asAcinetobacter baumanni, Group D Streptococci, VIRIDANS groupstreptococci, Citrobacter, Escherichia coli, Klebsiella, Enterococci, orStaphylococcus aureus.

The topical composition may comprise a solution, which may comprise asuspension, dispersion, or mixture; cream; oil; gel; ointment; lozenge;or gum as also described herein. Such dosage forms may be delivered, forexample, by application, dissolution, or irrigation at a body cavity ororifice or topically to skin or a mucosal surface, e.g., drops appliedto an ear, or a mouth rinse, wash, or gargle composition. In oneexample, the topical composition including cefixime and/ornitrofurantoin may be topically administered to infected skin formingthe outer body covering of a subject or to mucosal tissue of the vagina,oral cavity, respiratory tract, lungs, ear canal, or anus to treat amicrobial infection. For example, the topical composition may comprise asolution or suspension for topical administration in an ear, hand, foot,mouth using a bath or irrigation. In another example, the topicalcomposition comprises a nail lacquer for administration to nails. Insome embodiments, the topical composition may be utilized as a woundtreatment and administered to broken or unbroken skin or mucosal tissueas indicated above and elsewhere herein.

In various embodiments, a topical composition comprising cefixime and/ornitrofurantoin disclosed herein may comprise a solution for nasalirrigation, e.g., via Neil-Med® Irrigation Delivery; medium particlesize nasal delivery, e.g., via NasoNeb® Nasal Nebulizer; small particlesize nasal delivery, e.g., via PARI SinuStar™; small particle size lung(respiratory) delivery, e.g., via Omron® or PARI nebulizers; eardelivery; topical bath irrigation; topical spray application; topicalirrigation application; topical gauze application; or other topicalexternal application. For example, various embodiments comprising atopical treatment solution format including cefixime and/ornitrofurantoin may be administered via nasal irrigation delivery, nasaldelivery, ear delivery, bath irrigation, topical spray, gauze, ortopical irrigation. A bath irrigation may include submerging an infectedtissue surface or irrigating the infected tissue surface. In oneembodiment, a bath irrigation may be administered in a footbath, whichmay include a hand bath or soaking container, to treat or prevent aninfection. The method may include adding the topical composition to afootbath. In some embodiments, the method may include addition of acarrier comprising an aqueous diluent. The aqueous diluent may be inaddition to the carrier as described herein or may be the carrier. Forexample, a topical composition comprising a solution, cream, ointment,powder, gel, paste, or lotion format may be added to a footbath.Additional carrier comprising an aqueous diluent may also be added. Insome embodiments, the topical composition prior to addition of thediluent comprises a concentrated topical composition, and followingaddition of the carrier comprising the diluent, the topical compositioncomprises the percent compositions or weight described herein. Thefootbath solution may be agitated and/or heated in some embodiments. Afoot, hand, or other infected tissue surface may contact the footbathsolution in the footbath for administration of the topical composition.In one aspect, cefixime and/or nitrofurantoin may be combined with acarrier comprising a diluent wherein all or a portion of the diluent maybe selected from water, sodium chloride, saline, Dakin's solution,sodium hypochlorite, or combination thereof. In one example, the diluentcomprises sterile water for irrigation. Such a composition may beadministered to infected or wounded tissue such as skin, oral cavity,nasal cavity, respiratory system, anus, vagina, ear canal, hands, orfeet.

In some examples, the topical composition comprises a treatment solutionincluding cefixime and/or nitrofurantoin, such as powder from one ormore cefixime and/or nitrofurantoin capsules, in an amount describedherein without an additional antimicrobial pharmaceutical drug. Forexample, cefixime and/or nitrofurantoin capsule powder may be combinedwith a carrier or diluent to formulate a treatment solution format fornasal irrigation; topical bath irrigation, e.g., submersion; topicalspray application; topical irrigation application; topical gauzeapplication, or other topical external application, such as thosedescribed herein. The carrier or diluent may comprise an aqueoussolution, non-aqueous solution, sodium hypochlorite, Dakin's solution,water, sterile water, water for injection, water for irrigation,hydrogen peroxide, or sodium chloride, for example. In some embodiments,cefixime and/or nitrofurantoin is combined with a suitable amount ofcarrier diluent to obtain a daily dosage of cefixime and/ornitrofurantoin, typically 1 to 2 administration volumes; however,additional administration volumes may be used. The administrationvolumes may be as disclosed herein.

In various embodiments, the topical composition including cefiximeand/or nitrofurantoin is formulated for suppository administration at abody orifice, such as the rectum, vagina, or urethra. In someembodiments, the composition may comprise a dosage form including acapsule, tablet, gum, lozenge, or pouch configured for sublingual orsub-labial administration. The body cavities or orifices may compriseone or more of the nasal cavity, nostrils, tear duct, anus, vagina,urethra, mouth, and ear canal.

The topical composition including cefixime and/or nitrofurantoin may beprovided in an oral rinse solution or oral lozenge. The oral rinse maycomprise a mouthwash. Oral administration may also include applicationor an ointment, lotion, cream, or gel.

The topical composition comprising cefixime and/or nitrofurantoin may beutilized to treat infections of the lower or upper respiratory tract.The topical composition may be prepared for intranasal administrationsuch as a nasal solution, which may include a suspension or dispersion.The solution may be sprayed, inhaled, nebulized, or administered vialiquid stream lavage or nasal irrigation. Administration may be to thesinus cavity or the lungs. In various embodiments, other active agentsmay be added for purposes of alleviating other undesirable conditionsassociated with an administration such as anesthetics, analgesics,anti-inflammatories, antibacterial agents, antiviral agents andemollients. In one example, a mucolytic agent may be added. Mucolyticsare used to dissolve or breakdown mucus in the respiratory tract. In oneexample, the topical composition may include a mucolytic agent selectedfrom the group consisting of acetylcysteine, erdosteine, bromheksin,carbocisteine and guaifenesin or pharmaceutically acceptable saltsthereof. Excipients may be selected to assist in the release,dispersion, solubility, or the delivery of one or more of the activeagents at the administration or target site, e.g., skin, lungs,respiratory surfaces, or one or more body orifices. For example,excipients may include synthetic or naturally derived excipients such asone or more of a base, solvent, surfactant, permeation enhancer,emollient, humectant, disintegrate, acid, base, pH modifying agent orbuffer, solubility enhancer, or a carrier molecule or complex configuredto enhance or modulate diffusion, localization, targeting, active orpassive transport, or uptake, for example, of one or more active agents.Other pharmaceutically acceptable excipients or additives may include,for example, solvents, preservatives, flavorings, stabilizers (includingantioxidants), colorants, lubricant, sorbent, glident, filler, bulkingagent, and other additives used in preparations administered topicallyto skin, into the oral cavity, intranasally, or ear, or via the anus orvagina.

A nebulization format of the topical composition may comprise a dosagequantity of active agent within a suitable volume of carrier. In variousembodiments, the suitable volume is that which is suitable foradministration of the composition via nebulization. In one embodiment,the suitable volume is that which is suitable for administration via ina small volume nebulizer, which may be an intranasal nebulizer. Inanother embodiment, a suitable volume is that which is suitable fornasal irrigation. Intranasal administration via nebulization of thetopical composition may efficiently deliver the nebulized composition tothe respiratory tract, e.g., the nasal and paranasal sinus cavities.Once delivered, deposits of the active agents cefixime and/ornitrofurantoin, which may be in a concentrated state, may form onsurfaces of the respiratory tract. Nebulization may be by any suitablecommercially available nebulizer device, preferably an intranasalnebulizer. The active agents, such the cefixime and/or nitrofurantoin,may be mixed with the carrier to produce a nebulizer solution, which mayinclude a suspension/dispersion, dosage form for small particlenebulization using a small particle nebulization delivery system. Forexample, the nebulizer solution dosage form may be formulated forinhalational delivery to the lungs via a small particle size nebulizer,such as a PARI or Sinustar™, Omron, or other nebulizer configured tonebulize the dosage form to produce particles or droplets less than 10microns in size thereby allowing penetration into the lower respiratorytract, e.g., the lungs. In one embodiment, administration may comprisesmall particles or droplets, e.g., having aerosol characteristics,wherein the majority of the particles or droplets formed by thenebulization are less than 5 microns. In some embodiments, 60%, 70%,80%, or greater of the particles or droplets are less than 5 microns. Invarious embodiments, nebulization with a small particle nebulizerproduces nebulized aerosol particles wherein the majority of particlesare less than 10 microns, 8 microns, 5 microns, or 3 microns. In theseor other embodiments, the nebulized particles may be produced within aparticle size dispersion wherein at least 50%, 60%, 70%, 80%, 90%, or95% of the particles may be within about 3 microns and about 10 microns,about 3 microns and about 8 microns, about 3 microns and about 5microns, about 5 microns and about 8 microns, about 5 microns and about10 microns, or about 8 microns and about 10 microns. In someembodiments, the nebulized small particles may be inhaled into the upperairway and deposit thereafter at the paranasal sinus and nasal mucosa.In another embodiment, administration may include nebulization via alarge particle nebulizer, which may include intranasal administration.Administration via large particle nebulization may include particles ordroplets wherein a majority of such particles or droplets are largerthan about 5 microns, about 10 microns, about 15 microns, about 20microns or more, such as about 23 microns. In these or otherembodiments, the nebulized particles may be produced within a particlesize dispersion wherein at least 50%, 60%, 70%, 80%, 90%, or 95% of theparticles may be within about 10 microns and about 25 microns, about 10microns and about 20 microns, about 10 microns and about 15 microns,about 15 microns and about 25 microns, about 15 microns and about 20microns, or about 20 microns and about 25 microns. In variousembodiments, nebulized large particles may be inhaled intranasally intothe nasal and paranasal sinus cavities for deposition on the frontalrecess/sinus, spheno-ethmoid recess, ethmoid cavity, sphenoid andmaxillary sinuses, turbinates, middle meatus, and olfactory cleft. Largeparticle nebulization may utilize the active agents in a low volume baseto ensure high concentrations of actives remain in the nasal cavity ordeposit on respiratory surfaces in high concentration droplets. In oneembodiment, large particle nebulization is used to deliver anadministration volume of between about 0.2 mL to about 15 mL forretention in the nasal and paranasal sinus cavities.

The topical composition comprising cefixime and/or nitrofurantoin mayalso be utilized to treat an infection of the ear and be administered tothe same. For example, the topical composition may be utilized for auraladministration by instillation of a treatment solution into the earcanal.

As introduced above, the method of formulating the topical compositionmay include combining active agents in addition to the antimicrobialagent .g., cefixime and/or nitrofurantoin. In some embodiments, theadditional active agent comprises one or more active agents selectedfrom an anti-inflammatory agent, a steroid agent, an anti-allergicagent, an antidepressant agent, a stimulant agent, a disinfectant agent,an anticonvulsant agent, a local anesthetic agent, an anticonvulsantagent, a nerve depressant agent, a muscle relaxant agent, a NMDA(N-Methyl-D-aspartate) receptor antagonist agent, an opiate or opioidagonist agent, an NSAID agent, an analgesic agent, a keratolytic agent,or combination thereof.

It will be appreciated that topical compositions herein may include orspecifically exclude an additional active agent. It will also beappreciated that topical compositions may exclude an antimicrobial agentand rather include one or more of the additional active agents describedherein.

The method of formulating the topical composition comprising additionalactive agents may include combining all or a portion of an additionalactive agent from a powder format, e.g., from bulk powder, crushedtablet, injection powder, or other commercially available composition.In various embodiments, such additional active agents may be combinedwith the carrier together with or separate from all or a portion of theantimicrobial agent powder or other format. According to a method, allor a portion of an additional active agent may be provided in a formatselected from a solution, emulsion, gel, cream, lotion, ointment, orother format and may be combined with the carrier together with orseparate of all or a portion of the antimicrobial agent. In one example,all or a portion of the additional active agent may be mixed with all ora portion of the antimicrobial agent prior to being added to a carrier.In another example, the antimicrobial agent is added to the additionalactive agent that is provided in a commercially available medicatedcomposition comprising the carrier. In another example, theantimicrobial agent comprises a commercially available medicatedcomposition comprising all or a portion of the carrier to which theadditional active agent is combined. In another example, theantimicrobial agent comprises a commercially available medicatedcomposition comprising a portion of the carrier and the additionalactive agent comprises another portion of the carrier. In oneembodiment, any of the above formulations may include addition ofcarrier or components thereof that are not commercially availablemedicated compositions such as commercially available bases, liquidcarriers/vehicles such as aqueous and non-aqueous liquids, powders, orcomponents thereof, such as those identified herein.

In one embodiment, formulating the topical composition comprisescombining the antimicrobial agent with a commercially availablemedicated composition comprising all or a portion of the additionalactive agent.

In one embodiment, the method of formulating the topical compositioncomprises combining an antimicrobial agent and a nonsteroidalanti-inflammatory drug (NSAID) agent. In some examples, the method mayalso include combining a carrier. The NSAID agent may include one ormore NSAIDS selected from oxicams, such as meloxicam or piroxicam;salicylic acid derivatives, such as aspirin, diflunisal, salsalate, ortrilisate; propionic acids, such as flurbiprofen, ibuprofen, ketoprofen,naproxen, or oxaprozin; acetic acids, such as diclofenac, etodolac,indomethacin, ketorolac, nabumetone, sulindac, or tolmetin; fenamates,such as meclofenamate; and/or COX-2 inhibitors, such as celecoxib,rofecoxib, or valdecoxib. In various embodiments, the topicalcomposition may comprise between approximately 0.01% and approximately20% by weight NSAID agent.

In one embodiment, the method of formulating the topical compositioncomprises combining the antimicrobial agent, an NSAID agent identifiedherein, and a carrier in an amount sufficient to formulate the topicalcomposition comprising the antimicrobial agent in an amount betweenapproximately 0.01% and approximately 10% by weight, such as betweenapproximately 0.5% and approximately 5% or any other percent, percentrange, or percent therebetween by weight described herein and the NSAIDagent in an amount between approximately 0.01% and approximately 20% byweight, such as between approximately 2% and approximately 10% or anyother percent, percent range, or percent therebetween by weightdescribed herein. The antimicrobial agent may be or include anyantibacterial or antifungal active described herein. For example, in oneembodiment, the antimicrobial agent comprises an antifungal componentselected from itraconazole, ketoconazole, fluconazole, voriconazole, orcombination thereof. As a further or another example, the antimicrobialagent comprises an antibacterial component selected from levofloxacin,ciprofloxacin, linezolid, or combination thereof. Combining the NSAIDmay comprise adding a bulk powder, crushed tablet, or injection powder.As described above, the carrier may include an aqueous, organic, orinorganic solution, which may include a dispersion or suspension, cream,gel, ointment, lotion, emulsion, powder, or paste. The carrier may be acommercially available base vehicle for compounding or may be formulatedas indicated elsewhere herein. In one embodiment, the carrier comprisesa commercially available medicated composition comprising a portion ofthe antimicrobial or an additional active agent as described herein. Inone example, the carrier includes all or a portion of the NSAID agentand includes a commercially available medicated NSAID compositioncomprising a cream, ointment, suspension, lotion, gel, or solution. Forexample, the carrier may comprise a commercially available medicatedNSAID composition comprising a Diclofenac Sodium Solution. DiclofenacSodium Solution may contain, for example, 1.5% (w/w), diclofenac sodiumwherein each 1 mL of solution contains approximately 16.05 mg ofdiclofenac sodium. In one embodiment, the diclofenac solution comprisesa diclofenac sodium solution, 1.5% (w/w), such as that which ismanufactured under the trade name PENNSAID® by Nuvo Manufacturing,Varennes, Quebec, Canada or Diclofenac Sodium Topical Solution, 1.5%(w/w), manufactured by Apotex Inc. Toronto, Ontario, Canada M9L 1T9 forApotex Corp. Weston, Florida 33326 for treating the pain ofosteoarthritis of the knee. The diclofenac solution may also containvarious inactive ingredients such as dimethyl sulfoxide USP (DMSO, 45.5%w/w), ethanol, glycerin, propylene glycol and purified water. In oneembodiment, the diclofenac solution comprises a diclofenac sodiumsolution marketed under the trade name PENNSAID® and manufactured byNuvo Manufacturing, Varennes, Quebec, Canada, in a 2% (w/w) diclofenacsolution for treating the pain of osteoarthritis of the knee. Each gramof solution may contain approximately 20 mg of diclofenac sodium andvarious inactive ingredients such as dimethyl sulfoxide USP (DMSO, 45.5%w/w), ethanol, purified water, propylene glycol, and hydroxypropylcellulose. In other embodiments, other concentrations of diclofenacsolution, such as diclofenac sodium solutions, may be used.

In one embodiment, the method of formulating the topical compositioncomprises combining an antimicrobial agent and a local anesthetic agent.In some examples, the method may also include combining a carrier. Thelocal anesthetic agent may be selected from lidocaine, prilocaine,benzocaine, or combination thereof. The local anesthetic agent maycomprise between approximately 0.01% and approximately 15% by weight ofthe topical composition.

In one embodiment, the method of formulating the topical compositioncomprises combining the antimicrobial agent and a local anesthetic agentidentified herein in an amount sufficient to formulate the topicalcomposition comprising the antimicrobial agent in an amount betweenapproximately 0.01% and approximately 10% by weight, such as betweenapproximately 0.5% and approximately 5% or any other percent, percentrange, or percent therebetween by weight described herein and the localanesthetic agent in an amount between approximately 0.01% andapproximately 12% by weight, such as between approximately 2% andapproximately 10% or any other percent, percent range, or percenttherebetween by weight described herein. In some examples, the methodmay also include combining a carrier. The antimicrobial agent may be orinclude any antibacterial or antifungal active described herein. Forexample, in one embodiment, the antimicrobial agent comprises anantifungal component selected from itraconazole, ketoconazole,fluconazole, voriconazole, or combination thereof. As a further oranother example, the antimicrobial agent comprises an antibacterialcomponent selected from levofloxacin, ciprofloxacin, linezolid,cefixime, tetracycline, nitrofurantoin, or combination thereof.Combining the local anesthetic may comprise adding a bulk powder,capsule powder, crushed tablet, or injection powder. As described above,the carrier may include an aqueous, organic, or inorganic solution,which may include a dispersion or suspension, cream, gel, ointment,lotion, emulsion, powder, or paste. The carrier may be a commerciallyavailable base vehicle for compounding or may be formulated as indicatedelsewhere herein. In one embodiment, the carrier comprises acommercially available medicated composition comprising a portion of theantimicrobial agent or an additional active agent as described herein.In one example, the carrier includes all or a portion of the localanesthetic agent and includes a commercially available medicated localanesthetic composition comprising a cream, ointment, suspension, lotion,gel, or solution. For example, the carrier may comprise a commerciallyavailable medicated Lidocaine Ointment, Lidocaine Cream, Lidocaine andPrilocaine Cream, or Lidocaine Solution. In one instance, a method ofmaking the topical composition comprises combining the antimicrobialagent with a Lidocaine Solution including lidocaine in an aqueoussolution. The lidocaine solution may be a commercially availablelidocaine topical solution, such as lidocaine hydrochloride solution fortopical administration. The carrier may comprise the lidocaine solution.The lidocaine hydrochloride solution may contain, for example, 4%lidocaine (w/v) wherein each mL includes 40 mg lidocaine HCl. Forexample, in one embodiment, the lidocaine topical solution may beLidocaine Hydrochloride Topical Solution USP, 4% manufactured by IGILabs, Inc., Buena, N.J., in 50 mL screw cap glass bottles. The lidocainehydrochloride topical solution may contain various inactive ingredientssuch as methylparaben, purified water, and sodium hydroxide to adjust pHto 6.0-7.0.

In one embodiment, the method of formulating the topical compositioncomprises combining an antimicrobial agent, e.g., cefixime and/ornitrofurantoin, and a steroid agent. In some examples, the method mayalso include combining a carrier. In one example, the steroid agentcomprises a corticosteroid selected from amcinonide, betamethasonedipropionate, betamethasone valerate, clobetasol propionate,desoximetasone, diflorasone diacetate, flurandrenolide, fluticasonepropionate, fluocinonide, halcinonide, halobetasol propionate,mometasone furoate, triamcinolone acetonide, or combination thereof. Inanother example, the steroid agent comprises a corticosteroid selectedfrom betamethasone dipropionate, betamethasone valerate, clobetasolpropionate, fluticasone propionate, fluocinonide, halcinonide,halobetasol propionate, or combination thereof. In various embodiments,the topical composition comprises between approximately 0.001% andapproximately 1% by weight steroid agent.

In one embodiment, the method of formulating the topical compositioncomprises combining the antimicrobial agent, e.g., cefixime and/ornitrofurantoin, and a steroid agent identified herein in an amountsufficient to formulate the topical composition comprising theantimicrobial agent in an amount between approximately 0.01% andapproximately 10% by weight, such as between approximately 0.5% andapproximately 5% or any other percent, percent range, or percenttherebetween by weight described herein and the steroid agent in anamount between approximately 0.01% and approximately 2% by weight, suchas between approximately 0.05% and approximately 1% or any otherpercent, percent range, or percent therebetween by weight describedherein. In some examples, the method may also include combining acarrier. The antimicrobial agent may be or include any antibacterial orantifungal active described herein. For example, in one embodiment, theantimicrobial agent comprises an antifungal component selected fromitraconazole, ketoconazole, fluconazole, voriconazole, or combinationthereof. As a further or another example, the antimicrobial agentcomprises an antibacterial component selected from levofloxacin,ciprofloxacin, linezolid, cefixime, tetracycline, nitrofurantoin, orcombination thereof. Combining the steroid agent may comprise adding abulk powder, capsule powder, crushed tablet, or injection powder. Asdescribed above, the carrier may include an aqueous, organic, orinorganic solution, which may include a dispersion or suspension, cream,gel, ointment, lotion, emulsion, powder, or paste. The carrier may be acommercially available base vehicle for compounding or may be formulatedas indicated elsewhere herein. In one embodiment, the carrier comprisesa commercially available medicated composition comprising a portion ofthe antimicrobial agent or an additional active agent as describedherein. In one example, the carrier includes all or a portion of thesteroid agent and includes a commercially available medicated steroidcomposition comprising a cream, ointment, suspension, lotion, gel, orsolution. For example, the carrier may comprise a commercially availableClobetasol Propionate Cream, Foam, Gel, or Ointment, DiflorasoneDiacetate Cream or Ointment, Amcinonide Cream, Lotion, or Ointment,Betamethasone Dipropionate Cream, Lotion, Gel, or Ointment,Desoximetasone Cream or Ointment, Fluocinonide Cream, FluocinonideCream, Ointment, or Gel, Halcinonide Cream or Ointment, FluocinoloneAcetonide Cream, Ointment, Oil, or Solution, Halcinonide Cream orOintment, Betamethasone Valerate Cream, Lotion, or Ointment, DiflorasoneDiacetate Cream or Ointment, Triamcinolone Acetonide Cream or Ointment,Halobetasol Propionate Cream, Lotion, or Ointment, Desoximetasone Cream,Gel, or Ointment, Mometasone Furoate Cream or Ointment, FluticasonePropionate Cream, Flurandrenolide Cream, Lotion, or Ointment, orcombination thereof. In another example, the corticosteroid topicalcomposition is selected from Clobetasol Propionate Cream or Ointment,Diflorasone Diacetate Cream or Ointment, Amcinonide Cream or Ointment,Betamethasone Dipropionate Cream or Ointment, Desoximetasone Cream orOintment, Fluocinonide Cream or Ointment, Fluocinolone Acetonide Cream,Ointment, Oil, or Solution, Halcinonide Cream or Ointment, TriamcinoloneAcetonide Cream or Ointment, Halobetasol Propionate Cream or Ointment,Mometasone Furoate Cream or Ointment, Flurandrenolide Cream or Ointment,or combination thereof. In still another example, the carrier comprisesClobetasol Propionate Cream or Ointment, Fluocinonide Cream or Ointment,Fluocinolone Acetonide Cream, Ointment, Oil, or Solution, HalcinonideCream or Ointment, Halobetasol Propionate Cream, or Desoximetasone Creamor Ointment, Triamcinolone Acetonide Cream or Ointment, BetamethasoneDipropionate Cream or Ointment, or combination thereof. In anotherexample, the carrier comprises Clobetasol Propionate Cream, Foam, Gel,or Ointment, 0.05%, Diflorasone Diacetate Cream or Ointment, 0.05%,Amcinonide Cream, Lotion, or Ointment, 0.1%, Betamethasone DipropionateCream, Lotion, Gel, or Ointment 0.05%, Desoximetasone Cream or Ointment0.25%, Fluocinonide Cream 0.1%, Fluocinonide Cream, Ointment, or Gel,0.05%, Fluocinolone Acetonide Cream 0.01%, Fluocinolone Acetonide Cream0.025%, Fluocinolone Acetonide Oil 0.01%, Fluocinolone AcetonideOintment 0.01%, Fluocinolone Acetonide Ointment 0.025%, FluocinoloneAcetonide Solution 0.01%, Halcinonide Cream or Ointment, 0.1%,Betamethasone Valerate Cream, Lotion, or Ointment 0.1%, DiflorasoneDiacetate Cream or Ointment, 0.05%, Triamcinolone Acetonide Cream orOintment, 0.1%, Triamcinolone Acetonide Ointment, 0.05%, HalobetasolPropionate Cream, Lotion, or Ointment, 0.05%, Desoximetasone Cream, Gel,or Ointment 0.05%, Mometasone Furoate Cream or Ointment, 0.1%,Fluticasone Propionate Cream, 0.05%, Flurandrenolide Cream, Lotion, orOintment, 0.05%, or combination thereof. In still a further example ofthe above, the corticosteroid topical composition is selected fromClobetasol Propionate Cream or Ointment, 0.05%, Diflorasone DiacetateCream or Ointment, 0.05%, Amcinonide Cream or Ointment, 0.1%,Betamethasone Dipropionate Cream or Ointment 0.05%, Desoximetasone Creamor Ointment 0.25%, Fluocinonide Cream 0.1%, Fluocinonide Cream orOintment, 0.05%, Fluocinolone Acetonide Cream 0.01%, FluocinoloneAcetonide Cream 0.025%, Fluocinolone Acetonide Oil 0.01%, FluocinoloneAcetonide Ointment 0.01%, Fluocinolone Acetonide Ointment 0.025%,Fluocinolone Acetonide Solution 0.01%, Halcinonide Cream or Ointment,0.1%, Diflorasone Diacetate Cream or Ointment, 0.05%, TriamcinoloneAcetonide Cream, 0.1%, Halobetasol Propionate Cream or Ointment, 0.05%,Desoximetasone Cream or Ointment 0.05%, Mometasone

Attorney Docket No. 8138-73-9

Furoate Cream or Ointment, 0.1%, or Flurandrenolide Cream or Ointment,0.05%, or combination thereof. In still a further embodiment, thecorticosteroid topical composition is selected from BetamethasoneDipropionate Cream or Ointment 0.05%, Clobetasol Propionate Cream orOintment, 0.05%, Desoximetasone Cream or Ointment 0.25%, FluocinonideCream 0.1%, Fluocinonide Cream or Ointment, 0.05%, FluocinoloneAcetonide Cream 0.01%, Fluocinolone Acetonide Cream 0.025%, FluocinoloneAcetonide Oil 0.011%, Fluocinolone Acetonide Ointment 0.01%,Fluocinolone Acetonide Ointment 0.025%, Fluocinolone Acetonide Solution0.01%, Triamcinolone Acetonide Cream, 0.1%, Halobetasol PropionateCream, 0.05%, or Desoximetasone Cream or Ointment 0.05%, or combinationthereof.

In one embodiment, the method of formulating the topical compositioncomprises combining an antimicrobial agent, e.g., cefixime and/ornitrofurantoin, and an additional active agent selected from one or moremuscle relaxants, anticonvulsants, nerve depressants, NMDA receptorantagonists, opiates, opioid agonists, or combinations thereof. In someexamples, the method may also include combining a carrier. A musclerelaxant agent may comprise between approximately 0.001% andapproximately 5% by weight of the topical composition and be selectedfrom baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene,diazepam, metaxalone, methocarbamol, orphenadrine, quinine sulfate,tizanidine, or combination thereof; an anticonvulsant or nervedepressant agent may comprise between approximately 0.01% andapproximately 20% by weight of the topical composition and be selectedfrom gabapentin, topiramate, lamotrigine, or combinations thereof; aNMDA receptor antagonist agent may include ketamine; an opiate or opioidagonist agent may include tramadol, oxycodone, morphine, methadone,hydromorphone, fentanyl, hydrocodone, codeine, propoxyphene, butalbital,pentazocine, or combination thereof. The antimicrobial agent may becombined in an amount between approximately 0.01% and approximately 10%by weight of the topical composition, such as between approximately 0.5%and approximately 5% or any other percent, percent range, or percenttherebetween by weight described herein. The antimicrobial agent may beor include any antibacterial or antifungal active described herein. Forexample, in one embodiment, the antimicrobial agent comprises anantifungal component selected from itraconazole, ketoconazole,fluconazole, voriconazole, or combination thereof. As a further oranother example, the antimicrobial agent comprises an antibacterialcomponent selected from levofloxacin, ciprofloxacin, linezolid,cefixime, tetracycline, nitrofurantoin, or combination thereof.Combining the additional active agent may comprise adding a bulk powder,crushed tablet, or injection powder. As described above, the carrier mayinclude an aqueous, organic, or inorganic solution, which may include adispersion or suspension, cream, gel, ointment, lotion, emulsion,powder, or paste. The carrier may be a commercially available basevehicle for compounding or may be formulated as indicated elsewhereherein. In one embodiment, the carrier comprises a commerciallyavailable medicated composition comprising a portion of theantimicrobial agent or an additional active agent as described herein.In one example, the carrier includes all or a portion of the additionalactive agent and includes a commercially available medicated compositioncomprising the additional active agent in a cream, ointment, suspension,lotion, gel, or solution.

In one embodiment, the method of formulating the topical compositioncomprises combining an antimicrobial agent, e.g., cefixime and/ornitrofurantoin, and a keratolytic agent. In some examples, the methodmay also include combining a carrier. The keratolytic agent selectedform urea, salicylic acid, papain, or combinations thereof. For example,the topical composition may comprise the antimicrobial agent and urea.In various embodiments, the topical composition may comprise betweenapproximately 1% and approximately 30% by weight urea.

In one embodiment, the method of formulating the topical compositioncomprises combining the antimicrobial agent, e.g., cefixime and/ornitrofurantoin, and a keratolytic agent identified herein in an amountsufficient to formulate the topical composition comprising theantimicrobial agent in an amount between approximately 0.01% andapproximately 10% by weight, such as between approximately 0.5% andapproximately 5% or any other percent, percent range, or percenttherebetween by weight described herein and the keratolytic agent in anamount between approximately 5% and approximately 30% by weight, such asbetween approximately 10% and approximately 20% or any other percent,percent range, or percent therebetween by weight described herein. Theantimicrobial agent may be or include any antibacterial or antifungalactive described herein. For example, in one embodiment, theantimicrobial agent comprises an antifungal component selected fromitraconazole, ketoconazole, fluconazole, voriconazole, or combinationthereof. As a further or another example, the antimicrobial agentcomprises an antibacterial component selected from levofloxacin,ciprofloxacin, linezolid, cefixime, tetracycline, nitrofurantoin, orcombination thereof. Combining the keratolytic may comprise adding abulk powder, crushed tablet, e.g., crushed urea tablet, or injectionpowder. As described above, the carrier may include an aqueous, organic,or inorganic solution, which may include a dispersion or suspension,cream, gel, ointment, lotion, emulsion, powder, or paste. The carriermay be a commercially available base vehicle for compounding or may beformulated as indicated elsewhere herein. In one embodiment, the carriercomprises a commercially available medicated composition comprising aportion of the antimicrobial agent or an additional active agent asdescribed herein. In one example, the carrier includes all or a portionof the keratolytic agent and includes a commercially available medicatedkeratolytic comprising a urea ointment or cream. For example, thecarrier may comprise REA LO 40®, which is a 40.0% urea cream. Each gramof REA LO 40® contains 400 mg urea as the active ingredient and thefollowing inactive ingredients: purified water, emulsifying wax,glycerin, isopropyl myristate, sorbitol, neopentyl glycoldicaprylate/dicaprate, tridecyl stearate, tridecyl trimellitate anddimethyl isosorbide. The urea cream may comprise various percentages ofurea by weight (prior to compounding or prior to combination withanother carrier), such as 10%, 15%, 20%, 25%, 30%, 35%, 40%, or anyother commercially available percentage by weight. In variousembodiments, the urea cream may be Urix 40 Urea Cream marketed by TopixPharmaceuticals, Inc. Urix 40 Urea Cream includes 40% urea or 400 mgurea per gram and further includes Carbomer, Cyclomethicone, DimethiconeSilyate, Dimethiconol, Glycerin, Hydrogenated Lecithin, ImidazolidinylUrea, Petrolatum, Phenyl Trimethicone, Polyphosphorylcholine GlycolAcrylate, Triethanolamine, Water, and Xanthan Gum. In additionalembodiments, the urea cream may be Rea Lo 40 topical or Rea Lo 30topical marketed by Crown Laboratories. Rea Lo 40 topical comprises 400mg urea per gram and Rea Lo 30 topical comprises 300 mg urea per gram.Rea Lo 40 topical and Rea Lo 30 topical further include purified water,emulsifying wax, glycerin, isopropyl myristate, sorbitol, neopentyl,glycol dicaprylate/dicaprate, tridecyl stearate, tridecyl trimellitateand dimethyl isosorbide. In additional embodiments, the urea cream maybe Urea 10% Cream by Stratus Pharmaceuticals, Inc. Urea 10% Creamincludes 10% urea or 100 mg urea per gram, and further includesCarbomer, Fragrance, Isopropyl Myristate, Isopropyl Palmitate, PropyleneGlycol, Purified Water, Sodium Laureth Sulfate, Stearic Acid, Trolamineand Xanthan Gum. It is to be understood that the above urea creams (orany other urea cream) may be diluted or cut prior to or, in someembodiments, after compounding or otherwise combining the urea creamwith additional creams and/or actives. Thus, the topical composition maycomprise less urea by weight than was present in the urea cream prior tocompounding or combination with another cream and/or active.

The method of formulating a topical composition may comprise combiningan antimicrobial agent comprising crushed oral tablets and a carrier. Inone example, the antimicrobial agent comprises an antifungal componentcomprising voriconazole and the method of formulating the topicalcomposition comprises addition of a crushed voriconazole tablet to acarrier. The voriconazole tablets may comprise commercially availablevoriconazole 50 mg, 100 mg, 200 mg oral tablets. The oral tablets may becrushed and combined with the carrier to formulate a topical compositioncomprising between approximately 0.01% and approximately 20% by weight,approximately 0.05% and approximately 2%, approximately 0.1% andapproximately 2%, approximately 0.5% and approximately 2%, approximately1% and approximately 2%, or approximately 0.05%, approximately 0.1%,approximately 0.5%, approximately 1%, approximately 2%, approximately3%, approximately 4%, approximately 5%, less than approximately 5%,approximately 2% and approximately 7%, or greater than approximately 10%voriconazole by weight. To formulate a topical composition comprising adesired percent by weight voriconazole, the total desired weight of thetopical composition is subtracted from the weight of crushed oralvoriconazole tablet powder needed to obtain the desired percent byweight voriconazole. The weight of voriconazole tablet powder needed isdetermined by multiplying the weight of active needed to obtain thedesired percent by weight voriconazole in the topical composition. Forexample, a topical composition comprising 1% voriconazole may beformulated combining powder obtained from 200 mg oral voriconazoletablets. The weight of voriconazole tablet powder needed is determinedby multiplying the weight of voriconazole needed to obtain the desiredpercent by weight voriconazole in the topical composition. Here, a 1%voriconazole composition includes 10 mg voriconazole per gram. If a 200mg voriconazole tablet weights approximately 450 mg, 22.5 mg of crushedvoriconazole tablet powder comprises 10 mg voriconazole. Therefore, 22.5mg of crushed voriconazole tablet powder is combined for each gram oftopical composition. Consequently, 977.5 mg of carrier, and additionalactive agents, if any, may be combined with 22.5 mg of crushedvoriconazole tablet powder to formulate each gram of topical compositionto formulate a 1% by weight topical composition. Other percentcompositions may be formulated as described herein. The carrier maycomprise a suitable carrier selected to formulate a topical compositioncomprising a format selected from a cream, gel, lotion, ointment,emulsion (oil-in-water or water-in-oil), foam, solution, dispersion, orpowder, for example, suitable for topical application. In one example,the topical composition may be formulated for administration in avaginal or anal orifice. In one example, the topical compositioncomprises a solution or suspension for administration in a hand orfootbath or by irrigation. In another example, the topical compositioncomprises a nail lacquer for administration to nails. Further to theabove, the carrier may comprise components described herein forformulating the formats above or elsewhere herein. In an above oranother example, the carrier comprises a commercially availablecomposition comprising a base, such as those described herein. In anabove or another example, the carrier may comprise a commerciallyavailable medicated composition, such as those described herein.Additional active agents may include one or more antifungal actives,antibacterial actives, or both. Such additional antimicrobial agent maybe present in a combined amount between approximately 0.01% andapproximately 20% by weight, such as between approximately 0.01% andapproximately 5%. Additionally or alternatively, additional actives mayinclude other active agents such as one or more active agents selectedfrom an antiviral agent, an anti-inflammatory agent, a steroid, ananti-allergic agent, an antidepressant agent, a stimulant agent, adisinfectant agent, an anticonvulsant agent, a local anesthetic agent,an anticonvulsant agent, a nerve depressant agent, a muscle relaxantagent, a NMDA (N-Methyl-D-aspartate) receptor antagonist agent, anopiate or opioid agonist agent, an NSAID agent, an analgesic agent, akeratolytic agent, or combination thereof. Such additional active agentsmay be present in a combined amount between approximately 0.01% andapproximately 25% by weight, such as between approximately 1% andapproximately 10%.

In one example, the antimicrobial agent comprises an antifungalcomponent comprising fluconazole and the method of formulating thetopical composition comprises addition of a crushed fluconazole tabletto a carrier. The fluconazole tablets may comprise commerciallyavailable fluconazole 100 mg and/or 200 mg oral tablets. The oraltablets may be crushed and combined with the carrier to formulate atopical composition comprising between approximately 0.01% andapproximately 20% by weight, approximately 0.05% and approximately 2%,approximately 0.1% and approximately 2%, approximately 0.5% andapproximately 2%, approximately 1% and approximately 2%, orapproximately 0.05%, approximately 0.1%, approximately 0.5%,approximately 1%, approximately 2%, approximately 3%, approximately 4%,approximately 5%, less than approximately 5%, approximately 2% andapproximately 7%, or greater than approximately 10% fluconazole byweight. To formulate a topical composition comprising a desired percentby weight fluconazole, the total desired weight of the topicalcomposition is subtracted from the weight of crushed oral fluconazoletablet powder needed to obtain the desired percent by weight fluconazolein a manner similar to that described above with respect tovoriconazole. The carrier may comprise a suitable carrier selected toformulate a topical composition comprising a format selected from acream, gel, lotion, ointment, emulsion (oil-in-water or water-in-oil),foam, solution, dispersion, or powder, for example, suitable for topicalapplication. In one example, the topical composition may be formulatedfor administration in a vaginal or anal orifice. In one example, thetopical composition comprises a solution or suspension foradministration in a hand or footbath or by irrigation. In anotherexample, the topical composition comprises a nail lacquer foradministration to nails. Further to the above, the carrier may comprisecomponents described herein for formulating the formats above orelsewhere herein. In an above or another example, the carrier comprisesa commercially available composition comprising a base, such as thosedescribed herein. In an above or another example, the carrier maycomprise a commercially available medicated composition, such as thosedescribed herein. Additional active agents may include one or moreantifungal actives, antibacterial actives, or both. Such additionalantimicrobial agent may be present in a combined amount betweenapproximately 0.01% and approximately 20% by weight, such as betweenapproximately 0.01% and approximately 5%. Additionally or alternatively,additional actives may include other active agents such as one or moreactive agents selected from an antiviral agent, an anti-inflammatoryagent, a steroid, an anti-allergic agent, an antidepressant agent, astimulant agent, a disinfectant agent, an anticonvulsant agent, a localanesthetic agent, an anticonvulsant agent, a nerve depressant agent, amuscle relaxant agent, a NMDA (N-Methyl-D-aspartate) receptor antagonistagent, an opiate or opioid agonist agent, an NSAID agent, an analgesicagent, a keratolytic agent, or combination thereof. Such additionalactive agents may be present in a combined amount between approximately0.01% and approximately 25% by weight, such as between approximately 1%and approximately 10%.

In one example, the antimicrobial agent comprises an antibacterialcomponent comprising linezolid and the method of formulating the topicalcomposition comprises addition of a crushed linezolid tablet to acarrier. The linezolid tablets may comprise commercially availablelinezolid 600 mg oral tablets. The oral tablets may be crushed andcombined with the carrier to formulate a topical composition comprisingbetween approximately 0.01% and approximately 20% by weight,approximately 0.05% and approximately 2%, approximately 0.1% andapproximately 2%, approximately 0.5% and approximately 2%, approximately1% and approximately 2%, or approximately 0.05%, approximately 0.1%,approximately 0.5%, approximately 1%, approximately 2%, approximately3%, approximately 4%, approximately 5%, less than approximately 5%,approximately 2% and approximately 7%, or greater than approximately 10%linezolid by weight. To formulate a topical composition comprising adesired percent by weight linezolid, the total desired weight of thetopical composition is subtracted from the weight of crushed orallinezolid tablet powder needed to obtain the desired percent by weightlinezolid in a manner similar to that described above with respect tovoriconazole. The carrier may comprise a suitable carrier selected toformulate a topical composition comprising a format selected from acream, gel, lotion, ointment, emulsion (oil-in-water or water-in-oil),foam, solution, dispersion, or powder, for example, suitable for topicalapplication. In one example, the topical composition may be formulatedfor administration in a vaginal or anal orifice. In one example, thetopical composition comprises a solution or suspension foradministration in a hand or footbath or by irrigation. In anotherexample, the topical composition comprises a nail lacquer foradministration to nails. Further to the above, the carrier may comprisecomponents described herein for formulating the formats above orelsewhere herein. In an above or another example, the carrier comprisesa commercially available composition comprising a base, such as thosedescribed herein. In an above or another example, the carrier maycomprise a commercially available medicated composition, such as thosedescribed herein. Additional active agents may include one or moreantifungal actives, antibacterial actives, or both. Such additionalantimicrobial agent may be present in a combined amount betweenapproximately 0.01% and approximately 20% by weight, such as betweenapproximately 0.01% and approximately 5%. Additionally or alternatively,additional actives may include other active agents such as one or moreactive agents selected from an antiviral agent, an anti-inflammatoryagent, a steroid, an anti-allergic agent, an antidepressant agent, astimulant agent, a disinfectant agent, an anticonvulsant agent, a localanesthetic agent, an anticonvulsant agent, a nerve depressant agent, amuscle relaxant agent, a NMDA (N-Methyl-D-aspartate) receptor antagonistagent, an opiate or opioid agonist agent, an NSAID agent, an analgesicagent, a keratolytic agent, or combination thereof. Such additionalactive agents may be present in a combined amount between approximately0.01% and approximately 25% by weight, such as between approximately 1%and approximately 10%.

In one example, the antimicrobial agent comprises an antibacterialcomponent comprising levofloxacin and the method of formulating thetopical composition comprises addition of a crushed levofloxacin tabletto a carrier. The levofloxacin tablets may comprise commerciallyavailable levofloxacin 250 mg, 500 mg, 750 mg oral tablets. The oraltablets may be crushed and combined with the carrier to formulate atopical composition comprising between approximately 0.01% andapproximately 20% by weight, approximately 0.05% and approximately 2%,approximately 0.1% and approximately 2%, approximately 0.5% andapproximately 2%, approximately 1% and approximately 2%, orapproximately 0.05%, approximately 0.1%, approximately 0.5%,approximately 1%, approximately 2%, approximately 3%, approximately 4%,approximately 5%, less than approximately 5%, approximately 2% andapproximately 7%, or greater than approximately 10% levofloxacin byweight. Other embodiments may include commercially availablelevofloxacin bulk powder, levofloxacin oral solution, levofloxacin forinjection, or a combination thereof, instead of or together withlevofloxacin crushed tablets. To formulate a topical compositioncomprising a desired percent by weight levofloxacin, the total desiredweight of the topical composition is subtracted from the weight ofcrushed oral levofloxacin tablet powder needed to obtain the desiredpercent by weight levofloxacin in a manner similar to that describedabove with respect to voriconazole. The carrier may comprise a suitablecarrier selected to formulate a topical composition comprising a formatselected from a cream, gel, lotion, ointment, emulsion (oil-in-water orwater-in-oil), foam, solution, dispersion, or powder, for example,suitable for topical application. In one example, the topicalcomposition may be formulated for administration in a vaginal or analorifice. In one example, the topical composition comprises a solution orsuspension for administration in a hand or footbath or by irrigation. Inanother example, the topical composition comprises a nail lacquer foradministration to nails. Further to the above, the carrier may comprisecomponents described herein for formulating the formats above orelsewhere herein. In an above or another example, the carrier comprisesa commercially available composition comprising a base, such as thosedescribed herein. In an above or another example, the carrier maycomprise a commercially available medicated composition, such as thosedescribed herein. Additional active agents may include one or moreantifungal actives, antibacterial actives, or both. Such additionalantimicrobial agent may be present in a combined amount betweenapproximately 0.01% and approximately 20% by weight, such as betweenapproximately 0.01% and approximately 5%. Additionally or alternatively,additional actives may include other active agents such as one or moreactive agents selected from an antiviral agent, an anti-inflammatoryagent, a steroid, an anti-allergic agent, an antidepressant agent, astimulant agent, a disinfectant agent, an anticonvulsant agent, a localanesthetic agent, an anticonvulsant agent, a nerve depressant agent, amuscle relaxant agent, a NMDA (N-Methyl-D-aspartate) receptor antagonistagent, an opiate or opioid agonist agent, an NSAID agent, an analgesicagent, a keratolytic agent, or combination thereof. Such additionalactive agents may be present in a combined amount between approximately0.01% and approximately 25% by weight, such as between approximately 1%and approximately 10%.

In one example, the antimicrobial agent comprises an antibacterialcomponent comprising ciprofloxacin and the method of formulating thetopical composition comprises addition of a crushed ciprofloxacin tabletto a carrier. The ciprofloxacin tablets may comprise commerciallyavailable ciprofloxacin 250 mg, 500 mg, 750 mg oral tablets. The oraltablets may be crushed and combined with the carrier to formulate atopical composition comprising between approximately 0.01% andapproximately 20% by weight, approximately 0.05% and approximately 2%,approximately 0.1% and approximately 2%, approximately 0.5% andapproximately 2%, approximately 1% and approximately 2%, orapproximately 0.05%, approximately 0.1%, approximately 0.5%,approximately 1%, approximately 2%, approximately 3%, approximately 4%,approximately 5%, less than approximately 5%, approximately 2% andapproximately 7%, or greater than approximately 10% ciprofloxacin byweight. To formulate a topical composition comprising a desired percentby weight ciprofloxacin, the total desired weight of the topicalcomposition is subtracted from the weight of crushed oral ciprofloxacintablet powder needed to obtain the desired percent by weightciprofloxacin in a manner similar to that described above with respectto voriconazole. The carrier may comprise a suitable carrier selected toformulate a topical composition comprising a format selected from acream, gel, lotion, ointment, emulsion (oil-in-water or water-in-oil),foam, solution, dispersion, or powder, for example, suitable for topicalapplication. In one example, the topical composition may be formulatedfor administration in a vaginal or anal orifice. In one example, thetopical composition comprises a solution or suspension foradministration in a hand or footbath or by irrigation. In anotherexample, the topical composition comprises a nail lacquer foradministration to nails. Further to the above, the carrier may comprisecomponents described herein for formulating the formats above orelsewhere herein. In an above or another example, the carrier comprisesa commercially available composition comprising a base, such as thosedescribed herein. In an above or another example, the carrier maycomprise a commercially available medicated composition, such as thosedescribed herein. Additional active agents may include one or moreantifungal actives, antibacterial actives, or both. Such additionalantimicrobial agent may be present in a combined amount betweenapproximately 0.01% and approximately 20% by weight, such as betweenapproximately 0.01% and approximately 5%. Additionally or alternatively,additional actives may include other active agents such as one or moreactive agents selected from an antiviral agent, an anti-inflammatoryagent, a steroid, an anti-allergic agent, an antidepressant agent, astimulant agent, a disinfectant agent, an anticonvulsant agent, a localanesthetic agent, an anticonvulsant agent, a nerve depressant agent, amuscle relaxant agent, a NMDA (N-Methyl-D-aspartate) receptor antagonistagent, an opiate or opioid agonist agent, an NSAID agent, an analgesicagent, a keratolytic agent, or combination thereof. Such additionalactive agents may be present in a combined amount between approximately0.01% and approximately 25% by weight, such as between approximately 1%and approximately 10%.

According to a method of formulating the topical composition, whereinthe topical composition comprises a cream, the method may includecombining the antimicrobial agent, e.g., cefixime and/or nitrofurantoin,and a carrier to formulate a cream. The carrier may comprise a creambase, thickening agent, solvent, diluent, for example. In one example,the method includes combining a commercial medicated solution comprisingall or a portion of the antimicrobial agent and a carrier comprising abase cream or thickening agent. In another embodiment, the methodincludes combining a commercially available medicated cream comprisingall or a portion of the antimicrobial agent with an additional activeagent. In another embodiment, the method includes combining acommercially available medicated cream comprising a portion of theantimicrobial agent with a commercially medicated cream comprisinganother portion of the antimicrobial agent. In another embodiment, themethod includes combining a commercially available medicated creamcomprising all or a portion of the antimicrobial agent or an additionalactive agent with a commercially available medicated cream, ointment,solution, or powder comprising all or a portion of the antimicrobialagent or an additional active agent. Additional carrier components mayalso be added. In one example, the method includes combining anexcipient base powder comprising a blend of micronized xylitol andpoloxamers to make a homogeneous compounded composition. The combinedingredients may me mixed to form a smooth cream.

In an aspect, a treatment solution comprising levofloxacin as describedherein may be topically administered to an outer body region. The outerbody region may include an outer body surface such as skin or adjoiningtissues, which in some instances may be exposed through broken skin. Theouter body surface may be infected or be suspected of being infected. Inone example, the treatment solution may be topically administered to askin area by contacting a skin area that is or is suspected to beinfected by a bacterium or fungus. Contacting may include bathing, e.g.,submerging or irrigating, the skin area. The treatment solution may becontacted to damaged or undamaged skin. For example, the treatmentsolution may contact broken skin, underlying tissue, or both to bath thewounded area. Topical administration may include a bathingadministration, which may include submerging all or a portion of anouter body region or surface in the treatment solution, e.g., in a bathapplication or by irrigating all or a portion of the outer body region,or otherwise contacting all or a portion of the outer body region orsurface, such as by spraying, with the treatment solution in a sprayapplication. The outer body region may comprise skin such as a skinsurface a foot, hand, appendage, trunk, or portion thereof. Thetreatment solution may be topically administered, outside the body, fromthe external side of the body, to an affected body surface or underlyingtissue. For example, a foot, hand, or other body region may be placed ina bathing container or otherwise contacted with the treatment solutionin the bathing container for a suitable amount of time, e.g., 10 minutesor so, which may be repeated twice daily.

Methods of Treating or Preventing an Infection or Wound

The present disclosure also describes methods of treating an infectionor wound by providing or administering a topical composition describedherein. In some embodiments, the method may include formulating thetopical composition for topical treatment of an infection or wound. Thetreatment method may include contacting the topical composition to skin,nails, or body orifice that is infected or believed to be infected. Theinfection may be of an exterior surface of the body, an orifice, orinternal. Administration may include bath-irrigation, topical irrigationvia a syringe, administration in a topical powder, or a topical gel,cream, ointment, or lotion. Administration may be to an external surfaceof the body or to anal or vaginal surfaces. In various embodiments, thetopical composition may be administered via contact to an infected areasuch as to skin of a head, face, ears, nose, neck, shoulder, torso,chest, stomach, waistline, extremity, arm, hand, finger, nail, groin,buttock, leg, foot, or toe, for example. In an embodiment of a method totreat an internal infection, the topical composition may be administeredtopically as described herein wherein one or more active agents aretransdermally delivered locally or for systemic circulation. Additionalactive agents may be utilized in the topical composition to reduce pain,irritation, and inflammation such as NSAIDs, steroids, localanesthetics, anticonvulsants, antidepressants, for example. In variousembodiments, the topical composition may be administered 1 to 2 timesdaily or as otherwise needed.

In one embodiment, a topical composition may be used to treat aninfection or suspected infection accompanying a hyperkeratotic skinconditions that are marked by a thickening of the outer layers of skin.Methods of using the topical composition may include treating anindividual in need by topically applying the composition to affectedskin. Conditions treated may include conditions such as those marked bythickening of the skin, referred to as hyperkeratosis. The compoundedtopical composition described herein may thus be applied to suchaffected areas of the skin to treat the affected area. The compositionmay alleviate symptoms such as redness, swelling, or itching. Thecomposition may accelerate the healing process with respect to theaffected skin. In various embodiments, the topical composition may beadministered to treat hyperkeratotic conditions. The hyperkeratotic skincondition treated may include chronic eczema, corns, calluses, warts,seborrheic keratosis, lichen planus, actinic keratosis, as examples. Thehyperkeratotic skin conditions may be caused by irritation, such asphysical pressure or rubbing, chemical, infection, sunlight orradiation, or inherited conditions, for example. In an embodiment, thetopical composition may be administered to such affected skin in apreventative treatment regime to combat proliferation of microbialinfections with respect to the thickened skin layers. In some suchembodiments, the topical composition may include a keratolytic agent asdescribed herein.

Topical compositions comprising cream, lotion, paste, ointment, andsimilar formats may be applied by contact to skin, or mucosal tissuewith respect to anal or vaginal administration. In some embodiments, thetopical composition may be formulated in a shampoo carrier foradministration in a shampoo. In some formats, the composition may beadministered to an infected or target area via spray, drops, wash, swab,sponge, absorbent dressing, coating (e.g., a nail lacquer), soaking,submerging, footbath, instillation or irrigation. Embodiments comprisinga nail lacquer formulation may be applied directly to nails, to treat abacterial or fungal nail infection.

Various embodiments comprising a solution format may be administered ina footbath, which may include a hand bath or soak, to treat or preventan infection. The method may include adding the topical composition to afootbath. In some embodiments, the method may include addition of acarrier comprising an aqueous diluent. The aqueous diluent may be inaddition to the carrier as described herein or may be the carrier. Forexample, a topical composition comprising a solution, cream, ointment,powder, gel, paste, or lotion format may be added to a footbath.Additional carrier comprising an aqueous diluent may also be added. Insome embodiments, the topical composition prior to addition of thediluent comprises a concentrated topical composition, and followingaddition of the carrier comprising the diluent, the topical compositioncomprises the percent compositions described herein. The footbathsolution may be agitated and/or heated in some embodiments. A foot or ahand may contact the footbath solution in the footbath foradministration of the topical composition.

A footbath refers to a container that can hold some volume (e.g.,approximately 1.0 liters to approximately 30 liters) of a treatment orfootbath solution, which may typically be an aqueous solution orsuspension, and is designed to physically accommodate at least a portionof one or both feet of a subject. A footbath administration includesadministration of the topical composition utilizing a footbath. Afootbath may be used as a hand bath; however, smaller bathing containersmay typically be utilized as hand baths. In various embodiments,footbath solutions may be utilized as hand bath solutions. A footbathmay also be utilized for other body portions other than the hand orfoot, e.g., legs, arms, limbs, torso, scalp, ear, face, chest, or back.A footbath can comprise several features or agents that effect variousfunctions. For example, a footbath can comprise one or more lights orlight-emitting devices, a mechanical agitation agent (e.g., one or morejets or bubble makers) to physically agitate the enclosed water, abubble agent to create bubbles within the enclosed water, a heatingagent to heat the enclosed water, a vibration agent to vibrate theenclosed water (e.g., a high frequency vibration massage), an infrareddevice to provide infrared light to a foot or other body portion of thesubject within the bath, a massage agent (e.g., a roller) that providesmassaging contact to at least a portion of one or both feet, a pedicureagent that can clean or contact a foot or feet with a pumice, or acombination thereof. In an aspect, a footbath can have a waterfallelement. In an aspect, an agitation agent or an agitator can be coupledto both a motor and the footbath. In an aspect, a footbath can compriseone or more splashguards and other spill-resistant features to ensurethat the water remains enclosed within a container. A footbath may alsoaccommodate a subject's calves, meaning that the container is “deep” soas to allow the enclosed water to contact both the feet and at least aportion of the calves of the subject. Several manufacturers marketfootbaths including PIBB, Dr. Scholl's, Kendal, Conair (e.g., ModelFB5X, FB3, FB27R, FB30, FB52, etc.), and Brookstone.

A method of treating or preventing an infection may include formulatinga footbath solution comprising combining the antimicrobial agent and acarrier comprising a diluent. The carrier may comprise a liquid or drypowder diluent, base powder, cream, ointment, or other carrieridentified herein.

A method treating or preventing an infection may include formulating anirrigation solution comprising combining the antimicrobial agent and acarrier comprising a diluent. The carrier may comprise a liquid or drypowder diluent, base powder, cream, ointment, or other carrieridentified herein.

A method of treating a wound may include formulating a wound ointment,powder, cream, or solution comprising combining the antimicrobial agentand a carrier. The carrier may comprise a liquid or dry powder diluent,base powder, cream, ointment, or other carrier identified herein.

Formulating a topical composition comprising a solution for a footbath,irrigation, or spray may comprise adding the antimicrobial agent to acarrier comprising a diluent and agitating or mixing. The topicalcomposition may be administered in a footbath by contacting a skinsurface that is infected or suspected to be infected. The skin surfacemay be a hand, foot, limb, torso, or other surface identified herein.The topical composition may be administered in by irrigation by pouringonto skin or an orifice. In some embodiments, the skin or mucosal tissuecomprises a wound, which may include broken or unbroken tissue.

In various embodiments, the diluent may comprise an aqueous solution,non-aqueous solution, sodium hypochlorite, hydrogen peroxide, Dakin'ssolution, or sodium chloride. In an aspect, the amount of diluent can beapproximately 3.75 mL to approximately 60 mL. In an aspect, the amountof diluent can be approximately 15 mL. In some embodiments, the amountof diluent may be between 0.5 L and 5 L, or more, such as sufficientdiluent to achieve a desired volume, such as those identified elsewhereherein. In an aspect, the method can comprise adding to the diluent anexcipient base powder comprising a blend of micronized xylitol andpoloxamers. In an aspect, the excipient base powder can compriseLoxaSperse® excipient base powder. In an aspect, the excipient basepowder can comprise LoxaSperse® excipient base powder and XyliFos®excipient base powder. In an aspect, an excipient base powder can beobtained from a bulk source.

In an aspect, the subject has been diagnosed with or is suspected ofhaving a bacterial infection that affects exterior skin or mucosaltissue of the vaginal orifice or anus. In an aspect, the subject hasbeen diagnosed with or is suspected of having a fungal infectionexterior skin or mucosal tissue of the vaginal orifice or anus.

In an aspect, the subject can have diabetes. In an aspect, the subjectcan be obese. In an aspect, the subject can have poor blood flow. In anaspect, the subject can routinely wear thick socks. In an aspect, thesubject can routinely wear heavy boots, gloves, or clothing.

In some embodiments, a method of treating or preventing a, infectionassociated with a Candida, such as Candida albicans, Candida auris,Candida glabrata, Candida krusei, or Candida tropicalis may includetopically applying the topical composition to target skin or mucosalsurface. In some examples, the antimicrobial agent may comprise anantifungal component comprising an azole. In one example, the antifungalcomponent comprises itraconazole. In a further example, the topicalcomposition comprises itraconazole oral solution. In a further example,the topical composition comprises itraconazole oral solution and acarrier, such as a diluent or base for compounding. The topicalcomposition may also include one or more additional antifungal activedrugs, an antibacterial component, and/or one or more additional activeagents.

In an aspect, contacting can comprise placing at least part of the skinor mucosal tissue of the subject believed to be infected or of whichinfection is to be prevented in the footbath. In an aspect, contactingcan comprise placing at least part of one or both feet of the subject inthe footbath for approximately 5 to approximately 15 minutes.

In one embodiment, the method may include heating the solution containedwithin the footbath. In an aspect, a footbath can comprise a mechanicalagitation agent operable to mechanically agitate the enclosed solution,a heating agent to heat the enclosed solution, or both. Mechanicalagitation agents and/or means to agitate water within a compartment areknown to the art. In an aspect, a mechanical agitation agent can be amotorized agitation agent. In an aspect, an agitation agent or anagitator can be coupled to both a motor and the footbath. Motors andagitators are known to the art. In an aspect, mechanical agitation canserve to distribute the compounded composition throughout the watercontained within the footbath. Heating agents and/or means to heat waterin a compartment are known to the art.

In an embodiment, the topical composition comprises a nasal irrigationsolution comprising a carrier selected from an aqueous solution, water,or saline. The topical composition may comprise nitrofurantoin in anamount between approximately 25 mg and approximately 200 mg in anadministration volume. In another embodiment, the topical compositionmay comprise cefixime in an amount between approximately 200 mg andapproximately 400 mg in an administration volume. The topicalcomposition may usually be administered 1 to 2 times daily, but in someinstances may also be administered 3 times daily. Additional actives andcarrier components described herein may also be included.

In an embodiment, the topical composition comprises a nebulizationsolution comprising a carrier selected from an aqueous solution, water,or saline. The topical composition may comprise nitrofurantoin in anamount between approximately 25 mg and approximately 200 mg in anadministration volume. In another embodiment, the topical compositionmay comprise cefixime in an amount between approximately 200 mg andapproximately 400 mg in an administration volume. The topicalcomposition may usually be administered 1 to 2 times daily, but in someinstances may also be administered 3 times daily. Additional actives andcarrier components described herein may also be included.

In an embodiment, the topical composition comprises a solution for auraladministration comprising a carrier selected from an aqueous solution,water, or saline. The topical composition may comprise nitrofurantoin inan amount between approximately 25 mg and approximately 200 mg in anadministration volume. In another embodiment, the topical compositionmay comprise cefixime in an amount between approximately 200 mg andapproximately 400 mg in an administration volume. The topicalcomposition may usually be administered 1 to 2 times daily, but in someinstances may also be administered 3 times daily. Additional actives andcarrier components described herein may also be included.

In an embodiment, the topical composition comprises a bath or irrigationsolution comprising a carrier selected from an aqueous solution, water,saline, hydrogen peroxide, or sodium hypochlorite. The topicalcomposition may comprise nitrofurantoin in an amount betweenapproximately 25 mg and approximately 200 mg in an administrationvolume. In another embodiment, the topical composition may comprisecefixime in an amount between approximately 200 mg and approximately 400mg in an administration volume. The topical composition may usually beadministered 1 to 2 times daily, but in some instances may also beadministered 3 times daily. Additional actives and carrier componentsdescribed herein may also be included.

In an embodiment, the topical composition comprises a topical spraysolution comprising a carrier selected from an aqueous solution, water,saline, hydrogen peroxide, or sodium hypochlorite. The topicalcomposition may comprise nitrofurantoin in an amount betweenapproximately 25 mg and approximately 200 mg in an administrationvolume. In another embodiment, the topical composition may comprisecefixime in an amount between approximately 200 mg and approximately 400mg in an administration volume. The topical composition may usually beadministered 1 to 2 times daily, but in some instances may also beadministered 3 times daily. Additional actives and carrier componentsdescribed herein may also be included.

In an embodiment, the topical composition comprises a topical gauzesolution comprising a carrier selected from an aqueous solution, water,saline, hydrogen peroxide, or sodium hypochlorite. The topicalcomposition may comprise nitrofurantoin in an amount betweenapproximately 25 mg and approximately 200 mg in an administrationvolume. In another embodiment, the topical composition may comprisecefixime in an amount between approximately 200 mg and approximately 400mg in an administration volume. The topical composition may usually beadministered 1 to 2 times daily, but in some instances may also beadministered 3 times daily. Additional actives and carrier componentsdescribed herein may also be included.

In an embodiment, the topical composition comprises a nail lacquersolution or gel comprising a carrier selected from an aqueous solution,water, saline, hydrogen peroxide, or sodium hypochlorite. The topicalcomposition may comprise nitrofurantoin in an amount betweenapproximately 25 mg and approximately 200 mg in an administrationvolume. In another embodiment, the topical composition may comprisecefixime in an amount between approximately 200 mg and approximately 400mg in an administration volume. The topical composition may usually beadministered 1 to 2 times daily, but in some instances may also beadministered 3 times daily. Additional actives and carrier componentsdescribed herein may also be included.

References in the specification and concluding claims to parts by weightof a particular element or component in a composition denotes the weightrelationship between the element or component and any other elements orcomponents in the composition or article for which a part by weight isexpressed. Thus, in a compound containing 2 parts by weight of componentX and 5 parts by weight component Y, X and Y are present at a weightratio of 2:5, and are present in such ratio regardless of whetheradditional components are contained in the compound.

The term “contacting” as used herein refers to bringing one or moredisclosed compositions, disclosed compounded compositions, or disclosedantimicrobial agents together with water and an intended target (such asat least a portion of one or both feet of a subject) or targeted area(such as an area diagnosed with, suspected of having a bacterialinfection or a fungal infection, or susceptible to developing abacterial infection or a fungal infection) in such a manner that thedisclosed composition, a disclosed compounded composition, or adisclosed antimicrobial agent can exert an effect on the intended targetor targeted area either directly or indirectly. In an aspect,“contacting” means to insert or immerse at least a portion of one orboth feet of a subject into the water contained within a footbath.

The term “mixing” as used in a disclosed method of making a compoundedcomposition, for example, means to physically combine the recitedcomponents so as to achieve a homogeneous compounded composition (whichcan be a dry powder formulation). For example, in an aspect, anantibacterial component and an antifungal component can be mixed with anexcipient base powder; that is, an antibacterial component and anantifungal component are physically combined with an excipient basepowder and shaken, or stirred, or agitated so as to achieve ahomogeneous compounded composition. In an aspect, multiple recitedcomponents can be mixed together (i.e., antibacterial component, anantifungal component, an excipient base powder, and one or moreadditional antimicrobial agents (i.e., antibacterial component andantifungal component). In an aspect, “mixing” can also include siftingthe homogeneous compounded composition though a fine mesh strainer. Asuitable mixer is a TURBULA® mixer, which is able to mix powderysubstances with differing specific weights and particle sizes. Themixing can be generally performed for a pre-determined amount of time,i.e., for 10 seconds, 20 seconds, 30 seconds, 45 seconds, 1 minute, 5minute, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1hour, 2 hours, 3 hours, or more. A person skilled in the art couldascertain without undue experimentation, the amount of time required tomix the recited components so as to achieve a homogeneous compoundedcomposition.

Also, in an aspect, “mixing” can be used to describe the process ofmaking a solution by adding one or more of a disclosed compoundedcomposition, a disclosed composition, or a disclosed antimicrobial agentto a diluent. For example, mixing means to physically combine one ormore of a disclosed compounded composition, a disclosed composition, ora disclosed antimicrobial agent with a diluent.

“Mixing” can occur in a disclosed mixing container. In an aspect, amixing container can have a pre-determined size that can measure or holda pre-determined amount or volume. For example, in an aspect, a mixingcontainer can measure or hold an amount of approximately 1 ounces toapproximately 30 ounces. In an aspect, mixing container can measure orhold approximately 1 ounce, 2 ounces, 3 ounces, 4 ounces, 5 ounces, 6ounces, 7 ounces, 8 ounces, 9 ounces, 10 ounces, 11 ounces, 12 ounces,13 ounces, 14 ounces, 15 ounces, 16 ounces, 17 ounces, 18 ounces, 19ounces, 20 ounces, 21 ounces, 22 ounces, 23 ounces, 24 ounces, 25ounces, 26 ounces, 27 ounces, 28 ounces, 29 ounces, or 30 ounces. In anaspect, a mixing container can measure or hold approximately 6 ounces.In an aspect, a mixing container can measure or hold approximately 16ounces.

As used herein, the term “subject” refers to the target ofadministration, e.g., an animal. The term “subject” also includesdomesticated animals (e.g., cats, dogs, etc.), livestock (e.g., cattle,horses, pigs, sheep, goats, etc.), and laboratory animals (e.g., mouse,rabbit, rat, guinea pig, fruit fly, etc.). Thus, the subject of theherein disclosed methods can be a vertebrate, such as a mammal, a fish,a bird, a reptile, or an amphibian. Alternatively, the subject of theherein disclosed methods can be a human, non-human primate, horse, pig,rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term doesnot denote a particular age or sex. Thus, adult and newborn subjects, aswell as fetuses, whether male or female, are intended to be covered. Inan aspect, a subject can be a human patient. A subject can havediabetes. A subject can be obese. A subject can have circulatory issues.A subject can have a bacterial infection, be suspected of having abacterial infection, or be at risk of developing a bacterial infection.A subject can have a fungal infection, be suspected of having a fungalinfection, or be at risk of developing a fungal infection. For example,a subject can have damaged or moist skin, can have chronic disease, orcan be immunocompromised. A subject can have a bacterial infection and afungal infection, be suspected of having a bacterial infection and afungal infection, or be at risk of developing a bacterial infection anda fungal infection.

For example, a subject at risk of developing a bacterial infection canhave, for example, risk factors for developing a bacterial infection(e.g., have damaged or moist skin, have chronic disease, and/or beimmunocompromised). For example, a subject at risk for developing abacterial infection can be exposed to a bacterium or bacteria due toemployment (e.g., a health care worker) or due to the prevalence of abacterium or bacteria at a specific location (e.g., a hospital).

For example, a subject at risk of developing a fungal infection canhave, for example, risk factors for developing a fungal infection (e.g.,have damaged or moist skin, have chronic disease, and/or beimmunocompromised). For example, a subject at risk for developing afungal infection can be exposed to a fungus or fungi due to employment(e.g., a health care worker) or due to the prevalence of a fungus orfungi at a specific location (e.g., a hospital).

As used herein, the term “treatment” refers to the medical management ofa patient with the intent to cure, ameliorate, stabilize, or prevent adisease, pathological condition, or disorder (such as, for example, abacterial infection, a suspected bacterial infection, a fungalinfection, or a suspected fungal infection, or both). This term includesactive treatment, that is, treatment directed specifically toward theimprovement of a disease, pathological condition, or disorder, and alsoincludes causal treatment, that is, treatment directed toward removal ofthe cause of the associated disease, pathological condition, ordisorder. In addition, this term includes palliative treatment, that is,treatment designed for the relief of symptoms rather than the curing ofthe disease, pathological condition, or disorder; preventativetreatment, that is, treatment directed to minimizing or partially orcompletely inhibiting the development of the associated disease,pathological condition, or disorder; and supportive treatment, that is,treatment employed to supplement another specific therapy directedtoward the improvement of the associated disease, pathologicalcondition, or disorder. In various aspects, the term covers anytreatment of a subject, including a mammal (e.g., a human), andincludes: (i) preventing the disease from occurring in a subject thatcan be predisposed to the disease but has not yet been diagnosed ashaving it; (ii) inhibiting the disease, i.e., arresting its development;or (iii) relieving the disease, i.e., causing regression of the disease.

As used herein, the term “prevent” or “preventing” refers to precluding,averting, obviating, forestalling, stopping, or hindering something fromhappening, especially by advance action, but which may also beencompassed by treating.

As used herein, the term “diagnosed” means having been subjected to aphysical examination by a person of skill, for example, a physician, andfound to have a condition that can be diagnosed or treated by thecompounds, compositions, agents, or methods disclosed herein. Forexample, “diagnosed with a bacterial infection” means having beensubjected to a physical examination by a person of skill, for example, aphysician, and found to have a condition that can be diagnosed or can betreated by a disclosed compound or composition or agent that can preventor inhibit a bacterial infection. For example, “suspected of having abacterial infection” can mean having been subjected to a physicalexamination by a person of skill, for example, a physician, and found tohave a condition that can be likely be diagnosed as or can likely betreated by a disclosed compound or composition or agent that can preventor inhibit a bacterial infection, or it can mean that the subjectbelieves that he or she has a bacterial infection. For example,“diagnosed with a fungal infection” means having been subjected to aphysical examination by a person of skill, for example, a physician, andfound to have a condition that can be diagnosed or can be treated by adisclosed compound or composition or agent that can prevent or inhibit afungal infection. For example, “suspected of having a fungal infection”can mean having been subjected to a physical examination by a person ofskill, for example, a physician, and found to have a condition that canbe likely be diagnosed as or can likely be treated by a disclosedcompound or composition or agent that can prevent or inhibit a fungalinfection, or it can mean that the subject believes that he or she has afungal infection.

As used herein, the terms “administering” and “administration” refer toany method of providing a disclosed composition, compounded composition,antimicrobial agent, or a pharmaceutical preparation to a subject. Suchmethods are well known to those skilled in the art and include, but arenot limited to: oral administration, transdermal administration,administration by inhalation, nasal administration, topicaladministration, intravaginal administration, ophthalmic administration,intra-aural administration, intracerebral administration, rectaladministration, sublingual administration, buccal administration, andparenteral administration, including injectable such as intravenousadministration, intra-arterial administration, intramuscularadministration, and subcutaneous administration. Administration can becontinuous or intermittent. In various aspects, a disclosed composition,compounded composition, or antimicrobial agent can be administeredpharmaceutically; that is, administered to treat an existing disease orcondition. In further various aspects, a disclosed composition,compounded composition, or antimicrobial agent can be administeredprophylactically; that is, administered for prevention of a disease orcondition. In an aspect, the skilled person can determine an efficaciousdose, an efficacious schedule, and an efficacious route ofadministration for a disclosed composition, compounded composition, orantimicrobial agent so as to treat a subject or inhibit or prevent aninflammatory reaction. In an aspect, the skilled person can also alter,change, or modify an aspect of an administering step so as to improveefficacy of a disclosed composition, compounded composition, orantimicrobial agent. In an aspect, administering means contacting atleast a portion of one foot or both feet of a subject with agitatedwater comprising a disclosed composition, compounded composition, orantimicrobial agent in a footbath.

This specification has been written with reference to variousnon-limiting and non-exhaustive embodiments. However, it will berecognized by persons having ordinary skill in the art that varioussubstitutions, modifications, or combinations of any of the disclosedembodiments (or portions thereof) may be made within the scope of thisspecification. Thus, it is contemplated and understood that thisspecification supports additional embodiments not expressly set forth inthis specification. Such embodiments may be obtained, for example, bycombining, modifying, or reorganizing any of the disclosed steps,components, elements, features, aspects, characteristics, limitations,and the like, of the various non-limiting and non-exhaustive embodimentsdescribed in this specification.

Various elements described herein have been described as alternatives oralternative combinations, e.g., in a lists of selectable actives,ingredients, or compositions. It is to be appreciated that embodimentsmay include one, more, or all of any such elements. Thus, thisdescription includes embodiments of all such elements independently andembodiments including such elements in all combinations.

The grammatical articles “one”, “a”, “an”, and “the”, as used in thisspecification, are intended to include “at least one” or “one or more”,unless otherwise indicated. Thus, the articles are used in thisspecification to refer to one or more than one (i.e., to “at least one”)of the grammatical objects of the article. By way of example, “acomponent” means one or more components, and thus, possibly, more thanone component is contemplated and may be employed or used in anapplication of the described embodiments. Further, the use of a singularnoun includes the plural, and the use of a plural noun includes thesingular, unless the context of the usage requires otherwise.Additionally, the grammatical conjunctions “and” and “or” are usedherein according to accepted usage. By way of example, “x and y” refersto “x” and “y”. On the other hand, “x or y” refers to “x”, “y”, or both“x” and “y”, whereas “either x or y” refers to exclusivity.

Any numerical range recited herein includes all values and ranges fromthe lower value to the upper value. For example, if a concentrationrange is stated as 1% to 50%, it is intended that values such as 2% to40%, 10% to 30%, 1% to 3%, or 2%, 25%, 39% and the like, are expresslyenumerated in this specification. These are only examples of what isspecifically intended, and all possible combinations of numerical valuesand ranges between and including the lowest value and the highest valueenumerated are to be considered to be expressly stated in thisapplication. Numbers modified by the term “approximately” are intendedto include +/−10% of the number modified.

What is claimed is:
 1. A method of treating a bacterial infection of asubject, the method comprising: topically administering a topicalcomposition to the subject comprising contacting a tissue surface of thesubject to be treated with the topical composition, wherein the tissuesurface comprises skin or mucosal tissue, and wherein the topicalcomposition comprises nitrofurantoin combined with a carrier.
 2. Themethod of claim 1, wherein the topical composition is administered in adosage amount of between approximately 25 mg and approximately 200 mgnitrofurantoin.
 3. The method of claim 1, wherein the topicalcomposition is topically administered once or twice daily.
 4. The methodof claim 3, wherein the topical composition is topically administeredtwice daily and the topical composition comprises between approximately50 mg and approximately 200 mg nitrofurantoin in each topicaladministration.
 5. The method of claim 1, wherein the carrier comprisesan aqueous solution and the topical composition comprises a solutionformat.
 6. The method of claim 5, wherein the tissue surface comprisesan ear of the subject, and wherein administering the topical compositioncomprises administering the solution to an ear canal in one or moredrops.
 7. The method of claim 5, wherein the tissue surface comprises alung of the subject, and wherein administering the topical compositioncomprises nebulizing the solution for inhalation by the subject todeliver the topical composition to an infected mucosal tissue of thelung.
 8. The method of claim 5, wherein the tissue surface comprises anasal cavity of the subject, and wherein administering the topicalcomposition comprises contacting infected mucosal tissue of the nasalcavity via irrigation, spray, or nasal nebulization.
 9. The method ofclaim 5, wherein the tissue surface comprises a vagina or anus of thesubject, and wherein administering the topical composition comprisescontacting infected mucosal tissue of the vagina or anus with thesolution.
 10. The method of claim 5, wherein the tissue surfacecomprises a mouth of the subject, and wherein administering the topicalcomposition comprises contacting infected mucosal tissue of the mouthwith the solution.
 11. The method of claim 5, wherein the tissue surfacecomprises broken or unbroken skin of the subject, and whereinadministering the topical composition comprises spraying the solutiononto the infected skin surface, irrigating the infected skin surfacewith the solution, or submerging the infected skin surface in thesolution.
 12. The method of claim 1, wherein the carrier comprises anointment, cream, gel, or lotion and the topical composition isformulated in an ointment, cream, gel, or lotion format.
 13. The methodof claim 12, wherein the tissue surface comprises a vagina or anus ofthe subject, and wherein administering the topical composition comprisesapplying the ointment, cream, gel, or lotion onto the infected mucosaltissue of the vagina or anus.
 14. The method of claim 12, wherein thetissue surface comprises a mouth of the subject, and whereinadministering the topical composition comprises applying the ointment,cream, gel, or lotion onto infected mucosal tissue of the mouth.
 15. Themethod of claim 12, wherein the tissue surface comprises skin of thesubject, and wherein administering the topical composition comprisesapplying the ointment, cream, gel, or lotion onto the infected skinsurface.
 16. The method of claim 1, wherein the carrier comprises apowder and the topical composition comprises a powder format.
 17. Themethod of claim 16, wherein the tissue surface comprises mucosal tissue,and wherein administering the topical composition comprises applying thepowder onto the infected mucosal tis sue.
 18. The method of claim 16,wherein the infected mucosal tissue is mucosal tissue of the lungs,nasal cavity, mouth, vagina, or anus.
 19. The method of claim 16,wherein the tissue surface comprises skin of the subject, and whereinadministering the topical composition comprises applying the powder ontothe infected skin.